Traumatic Brain Inflammation

Traumatic Brain Inflammation
Inflammation is a reaction of tissues in response to any injury the human or vertebrae sustains.
Neuroinflammation is the inflammatory response by the glial cells that are present in the nervous
system along with neurons. It is an immune response to pathogen invasion or tissue damage most
likely to be caused by Infectious bacteria, Traumatic brain injury (TBI), or toxic metabolites. The
nervous system contains neurons and glial cells composed of astrocytes, microglia,
oligodendrocytes, ependymal cells in the Central nervous system (CNS), and Schwann cells,
satellite cells in Peripheral nervous system (PNS). The glial cells are non–neuronal cells that help to
form myelin, maintain homeostasis, provide support for neurons with nutrients, destroy ... Show
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The Experimental autoimmune encephalomyelitis (EAE) is the most commonly used model for
Multiple Sclerosis. The Multiple Sclerosis is a chronic inflammatory, neurodegenerative disease,
which is predominantly in young adults from ages 20–40 years. The immune response for this
inflammation is demyelination, axonal transection and eventually leading to cognitive deficits 4.
The EAE was induced to the mice via subcutaneous injection of 200 µg of auto–antigen myelin
oligodendrocyte glycoprotein (MOG) peptide 4. Then, the mice were tested for spatial learning and
memory tasks through the use of Barnes Maze method for both the control and EAE induced mice.
This method is a hippocampal behavioral task, where the mice must learn the spatial location of a
target hole to escape from the visual and auditory stimuli 4. After obtaining the brain tissue samples
from the mice, they were stained using Nissl Stain and later sectioned to evaluate branching and
spine count of the hippocampal CA1
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Rett Syndrome Analysis
Rett Syndrome (RTT) is a rare neurodevelopmental disorder caused by a mutation of a gene found
on the X chromosome; it have been thought that RTT was exclusively found in females, but a
limited number of males with RTT have been reported (Renieri et al, 2003). Unlike females, who
have two X chromosomes, males only have one X–chromosome. Because males lack a "backup"
copy of the X chromosome that can compensate for a faulty one, RTT is often fatal to males (Katz et
al, 2012). Prior research has shown that a mutation in the methyl CpG binding protein 2 (MeCP2)
gene predominantly causes RTT (Forbes–Lorman et al, 2014). The MeCP2 gene holds the
information for the production of the protein methyl cytosine binding protein 2 (MeCP2), which is
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Reduction in brain and neuronal sizes with an increase in cell density is consistently observed in
several brain regions of patients with RTT (Calfa et al, 2015). These areas include the cerebral
cortex, hypothalamus and the hippocampal formation (Belichenko et al, 2009). According to
Belichenko (2009) dendritic morphology of neurons has been observed in a number of
neurodevelopmental disorders, including RTT. An autoradiography done in the frontal cortex and
basal ganglia of individuals affected by RTT have shown complex abnormalities in the density of
glutamate receptors such as NMDA–(N–methyl–d–aspartate), AMPA–(α–amino–3–hydroxy–5–
methyl–4–isoxazolepropionic acid), kainate– and metabotropic receptors (Blue et al, 1999).The
prefrontal cortex of girls who were 2–8–year–old had increased NMDA receptors as compared to 10
year old girls who had reduced NMDA receptors. Receptor density was dependent on age of the
patient (Blue et al, 1999). Changes in the neurons, such as decreased dendrites and decreased
dendritic spine numbers are observed; particularly, changes in the hippocampal CA1 pyramidal
neurons are shown (Chapeau et al, 2012). When compared to an age–matched control, researchers
noticed that RTT affected patients had lower dendritic spine density in their

Chapter 11 Quizlet Anatomy
the ________ system controls brain and spinal cord central
The ________ nervous system controls the skeletal muscles. autonomic parasympathetic afferent
sympathetic somatic somatic
The part of the peripheral nervous system that carries sensory information to the CNS is designated
autonomic. motor. afferent. efferent. somatic. afferent
The efferent division of the peripheral nervous system innervates: glandular cells heart muscle cells
smooth muscle cells skeletal muscle cells All of the answers are correct. all
The most abundant class of neuron in the central nervous system is bipolar. unipolar. multipolar.
pseudopolar. anaxonic multipolar
The cytoplasm that surrounds the nucleus of a neuron is called the neuroplasm. ... Show more
content on Helpwriting.net ...
the endothelium of CNS capillaries forms a blood–brain barrier. endothelium of CNH capillaries
forms a blood–brain barrier
Extensive damage to oligodendrocytes in the CNS could result in loss of sensation and motor
control. loss of the structural framework of the brain. inability to produce scar tissue at the site of an
injury. decreased production of cerebrospinal fluid. a breakdown of the blood–brain barrier. loss of
sensation and motor control
Damage to ependymal cells would most likely affect the formation of myelin sheaths. formation of
cerebrospinal fluid. transport of neurotransmitters within axons. formation of ganglia. repair of
axons. formation of cerebrospinal fluid
The tiny gaps between adjacent Schwann cells are called ________ nodes of ranvier
Regions of the CNS with an abundance of myelinated axons constitute the ________ matter. white
After a stroke, what type of glial cell accumulates within the affected brain region? satellite cells
oligodendrocytes microglia ependymal cells Schwann cells microglia
The membranes of neurons at rest are very permeable to _____ but only slightly permeable to
_____. Na+; K+ Na+; Cl– K+; Na+ K+; Cl k, na
During depolarization, which gradient(s) move(s) Na+ into the cell? Na+ does not move into the
cell. Na+ moves out of the cell. only the electrical gradient both the electrical and chemical
gradients only the chemical gradient electrical and chemical gradients
What is the value for the

Ionotropic Receptors Research Paper
Ionotropic receptors is a binding site that opens when an ion attaches to the binding site. The
ionotropic receptor is also a direct method to the ion channels. Ionotropic receptors has a channel
where molecules move in and out of the ion channel. The ions that goes into the ion channel are
made out of sodium which cause the membrane to become small.
Metabotropic receptors is receptor that is a part of the binding site of a neurotransmitter.
Metabotropic is indirect and complex method to the ion channels. Metabotropic receptor process is
also different from the inotropic receptor. When the ion channel is open the molecule move to the
ion channel then molecule attaches to the metabotropic receptor and the ion channel closes.
Autonomic nervous system is a part of the different molecules in the body such as the smooth
muscle, cardiac muscle, gladder bladder, stomach, and urinary bladder. The neurophysiology is
showing the functions, the autonomic nervous system is showing how this works through the body.
There are two branches that are include in the autonomic nervous system. Those branches are called
the sympathetic and parasympathetic branches. ... Show more content on Helpwriting.net ...
The parasympathetic branch uses activity that is in the body which stores energy. For example, when
you eat something your saliva helps you to break down your food and when we swallow our food
the food goes into our stomach the fluid in our stomach helps to break down the food we eat which
gives us energy and is stored in our bodies. In this example, salvation is an example of one of the
activities that is in our book. The parasympathetic nervous system are located in the cranial nerves
and the spinal

Essay On Alzheimer's Pathophysiology
The pathophysiology, how the disease affects the body, is important when trying to understand
Alzheimer's. Damage to the brain in someone with Alzheimer's starts around a decade before
memory problems appear (NIH). Damage to the brain is symptom free during this period, but toxic
changes are occurring in the brain. Alzheimer's is mainly characterized by plaques and tangles in the
brain that form from abnormal deposits of proteins (NIH). Plaques form when beta–amyloid, protein
pieces, clump together (alz.org). Beta amyloid is chemically sticky and slowly accumulates between
nerve cells and eventually forms plaques (NIH). These plaques block cell to cell signaling at the
synapses (alz.org). In a normal and healthy brain, the brain is organized ... Show more content on
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The tracks are no longer straight, and they fall apart. As a result, supplies cannot move through cells,
and connections between cells are lost (alz.org). The lost connection between cells causes neurons to
die. Damage first takes place in the hippocampus, which is an area in the brain responsible for
memory. As more neurons die, other parts of the brain are affected. The brain tissue in the
hippocampus shrinks severely, as well as the cortex, affecting thinking, planning, and remembering
(alz.org). Chronic inflammation in the brain is another result from the disease. Research suggests
that it may be caused by the buildup of glial cells (NIH). In a healthy brain, microglia destroy waste
and toxins. In a damaged brain, microglia fail to engulf waste and protein collections, including
beta–amyloid plaques (NIH). It is unknown why microglia fail to do this, but one study that
researches are focusing on has to do with the TREM2 gene. In a healthy brain, TREM2 tells
microglia to destroy beta–amyloid plaques and also helps control inflammation in the brain, while in
a brain where this gene does not function normally, plaques build up in the brain outside of neurons

Eastern Equine Encephalitis Virus Case Study
Eastern Equine Encephalitis Virus (EEEV) is a highly pathogenic, positive–strand RNA arbovirus
belonging to the genus Alphavirus and family Togaviridae. The majority of infected individuals
experience sudden onset of fever, chills, headache, and decreased consciousness for several days1.
EEEV infection progresses rapidly to neurological disease with symptoms such as seizures,
paralysis or coma becoming visible 4–10 days after infection. Approximately 30–80% of people
infected with EEEV die, and the majority of those who recover are left with mild to extensive long–
term neurological damage1. There are currently no licensed vaccines or treatments available for
EEEV. Existing vaccines are limited to US military forces and laboratory researchers ... Show more
Microglia will be isolated from C57BL/6 mice and infected with WT EEEV and mutant EEEV.
qRT–PCR will be performed for EEEV mRNA levels at 6, 8, 12, and 24 hours. RAW.297
monocyte/macrophage cells or BHK–21 fibroblasts will be used as controls. We will also
knockdown miR–142–3p using a miRNA sponge as described previously. Flow cytometry will be
used to measure the proliferation of microglia in both infected and non–infected cells, and quantify
the expression of effector cytokines IL–6, IL–12, IL–16, and IL–23. We predict that high levels of
miR–142–3p are expressed and binding to EEEV's 3' UTR in microglia, which results degradation
of the EEEV genome. We also expect to observe increased activation and proliferation in microglia
infected with mutant EEEV or the

Microglial and Neurological Disorder
Microglial are the resident macrophage of the central nervous system (CNS) parenchyma that
participate in both CNS innate and adaptive immunity as well as taking part in many CNS
development and homeostasis maintenance to support brain integrity. Credited to these roles,
emerging evidence implicates microglial as key player that executing both beneficial and
detrimental effects in various CNS–related neurological disease including neurodegeneration,
neoplastic disease as well as neural development disorders.
Emerging evidence implicates microglial play critical roles to the CNS development of the brain.
Microglial are unique population arise from immature yolk–sac macrophages that migrate and
colonize the developing brain (Ginhoux et al., ... Show more content on Helpwriting.net ...
At adult normal physiological condition, microglial display surveillance or so–called 'resting'
phenotypes gauged by small cell body with extensively ramifying processes that actively surveying
the CNS microenvironment. In this steady state, the turnover processes is primarily confined and
well–maintained through local self–renewal of the long–lived resident microglial. Anomalies in the
CNS such as infections, tissues damage, and accumulation of abnormal protein or biochemical can
trigger microglial activation and in turn cause inflammation in CNS. Different from steady state,
inflammatory condition may have disrupted the integrity of blood brain barrier and allowed
recruitment of circulating myeloid cells and promotes their differentiation into microglial with more
potent inflammatory properties and resulting heterogeneity of microglial . Activated microglial
rapidly proliferate undergo phenotypic transition where they will exit from the 'resting' or 'surveying'
form and mounted inflammatory effectors functions. Evidences showed that activated microglial
capable of upregulated its phagocytose properties and secrete of inflammatory mediators
chemokines, cytokines, nitrite, reactive oxygen species, and free radicals to execute repair

Sub-Acute Phase
The response to a SCI can be separated into three discrete, partially overlapping phases: acute
(seconds to minutes after SCI), sub–acute (minutes to weeks after SCI), and chronic (months to
years after SCI). The acute phase centers around the primary SCI damage resulting from the trauma,
resulting in immediate physical and biochemical cellular changes. These include direct cell death,
vasospasms (leads to vasoconstriction, ischemia, and tissue death), plasma membrane compromise,
disruption of ionic homeostasis, and accumulation of neurotransmitters (26, 27). Many local
immune cells such as microglia, neutrophils, and astrocytes respond instantly. While some acute
events continue into the sub–acute phase (such as neurotransmitter and ionic dysregulation), the
sub–acute and chronic phases are defined by the ... Show more content on Helpwriting.net ...
The sub–acute phase continues from the acute phase and characterized by new events such as
formation of free radicals, delayed calcium influx, apoptotic cell death, inflammatory response,
central cavitation initiation, and astroglial scar initiation (28). Neutrophils are the first immune cells
to respond/arrive at injury, removing microbial intruders and tissue debris. Neutrophils release
protease metalloproteinase, ROS, TNF–α, IFN–γ, IL–1, 8, 12 and other pro–inflammatory factors to
activate other inflammatory and glial cells (29, 30). While initially beneficial, neutrophil persistence
significantly increases damage through continuous production of pro–inflammatory cytokines and
proteolytic enzymes (31). Therefore, neutrophil activation is limited to a couple days, and is
contained to the sub–acute phase. Microglia and macrophages become active in response to
neutrophils and the injury, also releasing numerous

Arginine Formation
In our previous study we came to the conclusion that excess and deprivation of arginine lead to
amyloid plaques being formed in yeast. We grew yeast with a dropout arginine broth, which allowed
us to use different concentrations of arginine. This showed us that amyloid like structures were
forming at excess and deprivation of arginine concentration meaning arginine is an essential
component to plaque formation. Then in a recent study by Duke University Medical Center, the
pathology of CVN–AD mice is driven by local immune suppression. The medical center had created
and used the unique CVN–AD mouse model of AD, in which immune–mediated nitric oxide is
lowered to mimic human levels, resulting in a mouse model that demonstrates the cardinal features
... Show more content on Helpwriting.net ...
First we will induce beta amyloid expression in the C. elegans and then quantify paralysis time.
Then the worms will be run on a series of assays, testing for arginine levels, arginase levels, and
NOS levels. We will then test to see if DFMO given before heat shock or after heat shock will
inhibit expression at a greater level. Whichever one works best we will then do the assays again. We
hypothesize that giving C. elegans a dose of DFMO prior to the heat shock will lead to less if not
totally inhibiting expression of beta–amyloids after the heat shock as well as increased levels of
arginine, and decreased levels of arginase and

Glia Research Paper
The term Glia is Greek in origin and means glue, this symbolic relationship between Glia's name,
and its function becomes ever more apparent when we learn that Glia cells secure the brain's
neurons together and protects them. Glial cells are crucial to the body's ability to maintain
homeostasis and contribute to almost all forms of homeostasis, such as regulating capillary flow,
maintaining the blood brain barrier, extracellular respiration, and can even provide lactate to the
neurons for energy. This essay will specifically be examining the Glia cells located within the
Central Nervous System.
One of the most common Glia cells in the brain is astrocytes, which promote the brains homeostasis
in copious ways. Astrocytes form around the synapses ... Show more content on Helpwriting.net ...
Microglia can be thought of as the guardians of the brain, and protect it from things such as disease.
Microglia cells are an essential element in the brains ability to sustain overall maintenance and
homeostasis, and constantly monitor the central nervous system for plaques, extra or damaged
neurons and synapses, as well as infectious agents. Essentially, Microglia can be thought of as the
brains first immune defense in the central nervous system. Microglia cells are phagocytic, which
means that they engulf bacteria and debris, which is so eloquently exemplified by the glymphatic
system. According to (Matcovitch–Natan et al. 2016) Microglia derives from erythromyeloid
progenitors that travel to the brain, which are thought to begin at embryonic day 8.5, and will
continue to do so until the blood brain barrier is fully formed. After this process occurs, self–renewal
will be the only source of new microglia in the brain. As the brain begins to develop, microglia need
to be adaptive to the changing needs of the brain, and will engage in synapse pruning, neurogeisis.
One of the first steps in pruning synapses

The Role of P2X Receptors in Nociception
Introduction
Nociception is the sensation of pain which is normally a warning signal to brain in respond to a
potential hazard. Generally noxious stimulations are detected by specialised high–threshold sensory
neurons, which are refer to nociceptors. The signals are then transferred to an electrical potential and
conducted to the brain via spinal cord. However sometimes abnormal nociception can lead to a
moderate to severe pain although a noxious stimulus is missing. This kind of pain are usually trigger
by nerve injury, while the pain sensation remains after the tissue had been healed. Although the
prevalence of neuropathic pain is not significant, about 7% to 8% of the European population is
affected, and about 5% are suffering severe pain (Torrance et al., 2006; Bouhassira et al., 2008).
Normally the neuropathic pain is induced by injury of somatosensory nerves, and the pain remains
after the tissue being healed. It can bring abnormal nociception while noxious stimuli are missing,
which called dysesthesia. Beside, pain can be triggered by non–painful stimuli, which is called
allodynia). Many research has linked the neuropathic pain to neuronal damages where endogenous
ATP being released. Therefore purinergic receptors that can respond to ATP are involved. In this
essay, after a brief introduction of P2X receptors, the role of microglial P2X4 and P2X7 in
neuropathic pain will be discussed.
Purinergic receptor can be divided into two families based on their different

Neurotoxic Roles In Alzheimer's Disease
Apart from microglia, certain lymphocyte subsets and myeloid cells express CX3CR1. Therefore,
Cells that express CX3CR1 i.e., monocytes and peripheral macrophages also undergo gene
rearrangement with TAM treatment (Yona et al., 2013) (Figure 3). However, most peripheral
myeloid cells that underwent Cre activation and rearrangements have a limited half–life and are
continuously replaced by CX3CR1neg bone marrow derived cells. Genetic modifications, such as
the activation of the YFP reporter gene or the deletion of "floxed" alleles are thus progressively lost
with time in these populations. In contrast, the resident microglia pool, without further input from
the BM, retains once introduced gene modifications. Thus, a singular induction of recombination, ...
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It is the most prevalent inflammation–mediated demyelinating disease in humans. MS is typically
characterized as a disease of the young adult, where approximately 10% of the diagnosed patients
will display symptoms that worsen over time, despite periods of remission. Initial clinical symptoms
begin with vertigo, fatigue, optic neuritis, and weakness in the limb extremities. The disease
progresses to further debilitating symptoms including ataxia, paraparesis, limb spasms, and
cognitive impairment (CA Davie et al., 1995; CH Polman et al., 2011; ND Chiaravalloti et al.,
2008). The neurodegeneration associated with MS occurs as lesions in the white matter of the CNS.
Specifically, the myelin sheath is damaged in MS by an autoimmune response. While the cause of
MS still is not fully understood, there is a clear inflammatory component. The T–cell subsets
involved in inflammatory reactions are mainly Th1 and Th17 (José Francisco Zambrano–Zaragoza
et al., 2014). The pathologic features of MS reflect a Th1–type delayed hypersensitivity reaction
consistent with a cell–mediated immune process (Sorensen et al., 1999). Several studies have shown
the involvement of Th17 cells and Th17 related cytokines like IL–17 in MS (G. Esendagli, 2013; V.
Brucklacher–Waldert, 2009; D. Vargas–Lowy, 2013) (Figure

Latest Alzheimer's Disease
Alzheimer's disease (AD) is a form of dementia that causes problems with memory, thinking, and
behavior. AD typically involves the development of a progressive neuropsychiatric disorder that is
characterized by gradual memory impairment, loss of acquired skills and emotional disturbances
(Lee, Y. J., Han, S. B., Nam, S. Y., Oh, K. W., & Hong, J. T.). Every 67 seconds an individual in the
United States develops AD. AD is the sixth leading cause of death in the United States. There are 5.3
million Americans diagnosed with AD (Latest Alzheimer's Facts and Figures). AD is one of the few
degenerative diseases that cannot be prevented, stopped, or cured (Latest Alzheimer's Facts and
Figures). Post–mortem examination of the brain of AD patients usually ... Show more content on
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2010). The neuroinflammation is an early, non–specific immune reaction to tissue damage or
pathogen invasion (Lee et al. 2010). Inflammation of the central nervous system (CNS) is
characterized by increased glial activation, pro–inflammatory cytokine concentration, blood–brain–
barrier permeability, and leukocyte invasion (Lee et al. 2010). Microglia are cells that support and
protect neuronal functions (Lee at al. 2010). They act as the first and main form of active immune
defense that orchestrate the endogenous immune response of the Central Nervous System. The
microglia play a central role in the cellular response to pathological lesions such as Aβ. Aβ can
attract and activate microglia, leading to clustering of microglia around Aβ deposits sites in the brain
(Lee et al. 2010). Even though microglia have neuroprotective functions, neurotoxic mechanisms
which involves continuous activation of microglia and toxic factors are released by microglia, which
may lead to neuroinflammation (Lee et al. 2010). Astrocytes (star–shaped glial cells) are the most
abundant cells in the brain and are located in the brain and spinal. Astrocytes have various functions
such as: biochemical support of endothelial cells of the BBB, supplying nutrients to the nervous
tissue, maintenance of extracellular ion balance, and healing the brain and spinal cord following
traumatic injury (Lee et al., 2010). Chemokines are released by astrocytes which attract microglia
and they further express proinflammatory products, thus increasing neuronal damage in the
pathogenesis of AD (Lee et al., 2010). Astrocytes play a critical role in Aß clearance and
degradation, and they also provide trophic support to neurons forming a protective barrier between
Aß deposits and neurons (Wyss–Coray et al., 2003). Neurons contribute to the production of

What Is The Importance Of The NE-Ergic System Degeneration...
Reductions in NE levels have been reported in brain regions receiving extensive (hippocampus) and
diffuse (frontal and temporal cortices, and cingulate gyrus) LC projections. The importance of such
biochemical studies are emphasized by the fact that these alterations correlate positively with the
duration and severity of the disease. LC neurons undergo significant degeneration and atrophy in
AD {Iversen, 1983 #35} (see {Simic, 2017 #108}
& {Phillips, 2016 #109}). While the degeneration of basal forebrain cholinergic neurons (BFCNs) in
AD has been the subject of intense study, it has been shown that the extent of NE–ergic system
degeneration in AD is more severe than that of the cholinergic system {Theofilas, 2015 #110}.
Notably, it has ... Show more content on Helpwriting.net ...
We found positive effects of xamoterol on cognitive function in mouse models of DS (Salehi et al.,
2009). While the molecular mechanisms behind this effect are yet to be elucidated, it has been
shown that chronic treatment of adult 5XFAD mouse model of AD with xamoterol can normalize
gene expression for a number of inflammatory factors including CD74, CD14 and TGFβ in the
cortex. In addition, the similar effects were found on immunoreactivity for amyloid (6E10) and early
neurofibrillary degeneration in these mice {Ardestani, 2017 #134}. 3. Neuroimmune system in
Alzheimer's disease and Down syndrome
The primary defense in the immune system are macrophages. The macrophage population in the
CNS comprises of microglia, perivascular macrophages, meningeal macrophages, and choroid
plexus macrophages. Microglia comprise around 10% of the cell population in the brain,but the ratio
of microglia to neurons varies among different brain regions {Sousa, 2017 #81}. Extensive recent
studies have indicated that these cells undergo dynamic alterations in their structure and function
during different pathophysiological processes. For this reason, these cells have been classified as
ramified microglia (physiological, typical of healthy CNS), dystrophic microglia (deterioration due
to age–related processes), and reactive microglia (hypertrophy due to acute injury). Dystrophic
microglia play an important role particularly in the context of

Overview Of Glial Activation And Proinflammatory Biobioce
12. Zhu 2014 Quetiapine attenuates glial activation and proinflammatory cytokines in APP/PS1
transgenic mice via inhibition of nuclear factor–κB pathway. Abstract Background: In Alzheimer's
disease, growing evidence has shown that uncontrolled glial activation and neuroinflammation may
contribute independently to neurodegeneration. Antiinflammatory strategies might provide benefits
for this devastating disease. The aims of the present study are to address the issue of whether glial
activation and proinflammatory cytokine increases could be modulated by quetiapine in vivo and in
vitro and to explore the underlying mechanism. Methods: Four–month–old amyloid precursor
protein (APP) and presenilin 1 (PS1) transgenic and nontransgenic mice were ... Show more content
on Helpwriting.net ...
Apart from these classic hallmarks, increasing evidence has demonstrated uncontrolled glial
activation and neuroinflammation in AD brain may contribute independently to neural dysfunction
and cell death (Akiyama et al., 2000; Wyss–Coray and Mucke, 2002). Robust activation of
microglia has been found in and around the area of amyloid plaques in the AD brain, and reactive
astrocytes have been shown to form a halo surrounding the amyloid plaques (Itagaki et al., 1989; Ho
et al., 2005). Additionally, numerous proinflammatory factors have been reported to be elevated in
both patients with AD and transgenic animal models of AD (Griffin et al., 1989; Akiyama et al.,
2000; Ruan et al., 2009). Whether alleviation of neuroinflammation will offer therapeutic benefit for
AD remains unclear. Epidemiological studies show a possible association between suppression of
inflammation and reduced risk for AD (in t' Veld et al., 2001; Vlad et al., 2008). Therefore, drugs
targeting neuroinflammation might provide benefits for the prevention and treatment of this
devastating disease. In the central nervous system, microglia and astrocytes are the major type of
glial cells, and activation of these cells has been involved in all neurodegenerative diseases (Wyss–
Coray and Mucke, 2002). Nevertheless, the diverse physiological functions of glial activation might
complicate the interpretation of experimental

Ischemic Brain Stroke Research Paper
Ischemic brain stroke represents the most common cause of serious morbidity and the second most
common cause of mortality worldwide. Along with that traumatic brain injury also contributes a
significant number of mortality and morbidity. While spontaneous recovery of lost functions to a
certain degree takes place in some patients, the majority never regain full functional independence
and ultimately suffer from a reduced quality of life. Clearly these health burden seeks detailed
exploration of clinical and pathological aspects to modify the present treatment strategies. Glial scar
formation which constitutes reactive astrocytes, microglia, endothelial cells, fibroblasts and
extracellular components is the response of CNS after external assault.

The Role Of Cytokines On Immune Privilege
THE ROLE OF CYTOKINES IN MAINTAINING IMMUNE PRIVILEGE IN THE BRAIN
Review By Ifunanya Ezechukwu
1. Introduction
Immune privilege sites are regions of the body which are able to tolerate the introduction of foreign
antigens without producing an inflammatory response [1]. It is an active process and these sites are
believed to have emerged in order to protect susceptible parts of the body which aren't able to
regenerate their tissues and have crucial bodily functions [2].Most likely, inflammation in such body
parts could lead to a total loss of function. The type of segregation of immunologically privileged
sites from the rest of the body's immune system can lead to them becoming targets of autoimmune
diseases. Immune privilege can be innate, as well as acquired. The feedback from the innate section
serves as the first line of defence, and it comprises of a stable connection of resident specialized
cells (e.g. astrocytes, microglia etc). These cells encompass the tissues they protect with elongated
processes that are sensitive to any changes in that particular environment [27]. The second form of
defence is acquired, handled by particular groups of T–cells which able to cross the protective
barriers of the tissues. There is an active rejection of cells by CD4 T–cells, even when the cell may
display harmful antigens [3], because T–cells become pathogenic if they begin to recognise local

Early Life Stress Experiments
The hypothesis proposed was finding how the brain is rewired to cause depression. The hypotheses
tested involved finding how chronic early–life stress can impact adult emotional function, and what
roles do microglial cells have in rewiring the brain. The experiments conducted used mice in two
groups, an experimental group that underwent chronic early life stress and a control. Hormone
production analysis for each subject occurred as the experiment proceeded. The mice underwent
object recognition tasks, followed by sucrose and forced swim tests to quantify the effects of
depression and anhedonia. Reduction of CRH production then occurred via short–hairpin RNA
intervention in target mice. The mice were then retested, and given a social play test. The
experiment then analyzed the synapse function of the control and CES mice. Cell imaging
determined neuron expression, with further testing being conducted that focused on the analysis of
microglial cells in a developing fetus. ... Show more content on Helpwriting.net ...
The CES mice in comparison to the control possessed memory deficits and a lower preference for
sucrose, and were quicker to become immobile in water. Short–hairpin treatment reduced the effects
of chronic stresses. CES mice behavior after treatment resembled the control, showing no memory
deficits, and an increase preference for sucrose. Analysis on neuron function of the mice determined
that early life experiences alter the programming of stress–sensitive CRH expressing neurons. Early
life stresses were found to impair the function of microglia, which phagocytize excess synapses in
developing

Understanding the Brain: Synaptic Pruning Essay example
Synaptic Pruning Synaptic pruning, or synaptic elimination, is an essential aspect of the
development of the brain; when the brain destroys itself, removing unwanted synapses, neurons or
neuronal configurations to increase efficiency of connections. The process and timing of pruning is
thought to be significantly changed by the experiences, genes, and even the thoughts of the
developing mind. There are a variety of theories as to the true nature of pruning. During early
childhood, there is a huge proliferation of connections between neurons, usually peaking around the
age of two. The adolescent brain then cuts down the amount of connections, deciding which ones
are important to keep and which can be let go. While there are various ... Show more content on
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Some neuroscientists have made educated guesses as to the nature of this deletion, and there has
been relative consensus that microglia, being part of the immune system, remove the synapses
because they appear to be either unnecessary or damaged. This abnormal synaptic pruning could be
a significant source of the symptoms of schizophrenia. If this mutation is genetic, then perhaps it
could be corrected by sophisticated forms of genetic engineering. Loose associations have also been
found between the genes that influence synaptic pruning and those that influence autism and
Aspergers disorder. Pruning is also highly dependent on experience [4]. Neural plasticity reaches its
peak during childhood and before synaptic pruning begins. Thus, if a child begins to learn a
language or any other complex function before synaptic pruning, that function will be deemed
important and the neural connections pertaining to it will be kept and strengthened. This gives new
meaning to the saying "use it or lose it." Experiences during and before synaptic pruning are perhaps
some of the most important in development, because they directly affect brain function for the rest
of the subject's life. It is thought that connections deleted during pruning cannot be regained. "The
fact that there are more connections [in a child's brain] allows things to be moved around," said
physiologist Ian Campbell from the

Essay On Phencyclidine
Chronic phencyclidine induces inflammatory responses and activates GSK3β in mice. Use of
phencyclidine (PCP) in rodents can mimic some aspects of schizophrenia. However, the underlying
mechanism is still unclear. Growing evidence indicates that neuroinflammation plays a significant
role in the pathophysiology of schizophrenia. In this study, we focused on inflammatory responses
as target of PCP for inducing schizophrenia–like symptoms. 3–month–old C57BL/6J mice received
daily injections of PCP (20 mg/kg, i.p.) or saline for one week. PCP–injected mice produced
schizophrenia–like behaviours including impaired spatial short–term memory assessed by the Y–
maze task and sensorimotor gating deficits in a prepulse inhibition task. Simultaneously, ... Show
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Therefore, the pathological process underlying schizophrenia may involve neuroinflammatory
responses in the central nervous system (CNS).
Noncompetitive N–methyl–d–aspartate (NMDA) receptor antagonists, including phencyclidine
(PCP), evoke schizophrenia–like psychosis and cognitive deficits in healthy humans [10, 11] and
similar cognitive deficits and hyperlocomotion related to positive symptoms in rodents [12, 13, 14,
15]. Studies on the behavioural deficits induced by PCP have focused on its possible mechanism in
disrupting glutamatergic NMDA neurotransmission leading to neuronal degeneration [16]. One
study has shown that there was an increased expression of glial fibrillary acidic protein (GFAP) after
chronic PCP administration in rats [17]. Therefore, it is important to address the neuroinflammatory
changes in the PCP–induced mouse model of schizophrenia.
Glycogen synthase kinase–3β (GSK3β) is a key regulator in various physiological pathways,
including protein synthesis, cell differentiation, apoptosis and cell survival [18]. It has been
demonstrated that GSK3β signaling is impaired in schizophrenia [19]. Furthermore, GSK3β
inhibition attenuates activation of the proinflammatory transcription factor nuclear factor kappa B
(NFκB), as well as the resulting effects on NFκB–mediated gene expression, indicating that GSK3β

A Study On Rett Syndrome ( Rtt )
Rett Syndrome (RTT) is a rare neurodevelopmental disorder caused by a mutation of a gene on the
X chromosome and therefore, more commonly found in females (Renieri et al, 2003). A limited
number of cases have been documented in males (Katz et al, 2012). Prior research has shown that a
mutation in the methyl CpG binding protein 2 (MeCP2) gene predominantly causes RTT (Forbes–
Lorman et al, 2014). The MeCP2 gene holds the information for the production of the protein
methyl cytosine binding protein 2 (MeCP2), which is required for brain development (Gonzales &
LaSalle, 2010). When the MeCP2 gene mutates, it leads to a decline in cognitive development
(Renieri et al, 2003). Decline in physical development such as microcephaly, and respiratory ...
The last stage, stage four, the motor deteriorations stage of RTT is categorized by reduced mobility
(Pohodich & Zoghbi, 2015). RTT falls under the autism spectrum disorder (ASD) as being
neurodevelopmental debilitation, and is it the most incapacitating ASD classification because it is
diagnosed almost entirely in females (Gadalla et al, 2011). Developing research shows that RTT is a
consequence of a discrepancy in the development of the synapses in the brain, and that MeCP2 is
important for the growth of synapses and neurons during development. Presently, researchers are
trying to understand the mechanisms that mediate the phenotypic features of RTT. To explore the
mechanisms, researchers have created genetic mouse models of RTT to study the neuropathology of
RTT including glutamate dysfunction and neuroinflammation (Maezawa & Jin, 2010). In this
literature review, I am going to delve into the genetic mouse models of RTT and how they relate to
RTT in humans, such as the phenotypic features, the neuropathy of RTT, such as neuroinflammation
and glutamate regulation, and treatments of neuroinflammation. This review will also focus on the
targeting of microglia and astrocytes using nanotherapeutics, and specifically dendrimer–based
treatments in several animal models of neuroinflammation. Currently, there is no known cure or
treatments directed at the underlying neuropathology of RTT, and so there is a need for further

Most Common Cause Of Alzheimer's Disease (AD)
Alzheimer's disease (AD) results in an impairment on the cognitive dimension of the patients. The
hallmarks of AD brains are irrevocably the presence of Aβ peptides and hyperphosphorylated tau
protein within the brain. However, neuroinflammation is being intrinsically associated with
cognitive impairments in AD. Previously we have found an increase on type I interferon (IFN)
expression at early ages on a transgenic AD mice model, which raises the possibility of altered
immune responses throughout the disease. Herein we tested the effect of the blockage of type I IFN
response, through the injection of an antibody against the IFN type I receptor (α–IFNAR1), on the
cognitive performance and AD pathology. Surprisingly we found that control IgG ... Show more
Microglia, in the same way as vascular cells, can bind to Aβ resulting in an amplified production of
cytokines, glutamate and nitric oxide (6, 7). Some studies suggest that chemokines can recruit
monocytes from the peripheral blood into plaque bearing brain.(8) Related to this
neuroinflammation are the alterations of type I and type II Interferon (IFN) levels in AD mice
model, PDGFB–APPSwInd (J20), where an enhanced type I IFN signaling at the brain barriers and
hippocampus, and decreased type II IFN response, only at the barriers were observed.(9) Of interest
the blockage of IFN type I response at the central nervous system is able to partial revert the
cognitive decline in aged mice.(10) However the role of this blockage on an AD mice model is still

Effects Of Exposure On Tobacco Smoke
The adverse effects of exposure to tobacco smoke while in utero and during early childhood are well
documented, with detrimental consequences occurring within the lungs and brain, resulting in
decreased intelligence and behavioural changes, such as heightened excitability (1,2). Tobacco
smoke exposure occurs prenatally from smoking mothers, or postnatally by environmental tobacco
exposure, and has been associated with low birth weight and head circumference, and creates
vasoconstriction resulting in reduced blood flow to the uterus, initiating oxygen and nutrient
deprivation (1). Additionally, tobacco smoke targets the developing nervous system, resulting in cell
proliferation and differentiation alterations in utero, and abnormal synaptic activity during infancy
(1). Synapses regulate intercellular communication within the brain, and are formed via a variety of
guidance cues and recognition signals, which direct outgrowing axons precisely to the target cell (3),
with abnormal activity ultimately leading to cell loss and neuronal damage (1).
Polycyclic aromatic hydrocarbons (PAH), a compound found within tobacco smoke (4), are toxic,
carcinogenic and neurotoxic (5), and are also a common air pollutant generated during the
incomplete combustion of organic material, such as coal, diesel and gasoline (5). While lead and
mercury, also released in coal burning, are likewise developmental neurotoxins (6). Exposure to
PAH creates PAH–DNA adducts, which reflect an individual's

Glial Cells Essay
Glial cells are the most numerous cells in the brain, outnumbering neurons nearly 3:1, although
smaller and some lacking axonal and dendritic projections. Once thought to play a subpar role to
neurons, glial cells are now recognized as responsible for much greater functions. There are many
types of glial cells, including: oligodendrocytes, microglia, and astrocytes. Oligodendrocytes form
the myelin sheath in the CNS, by wrapping themselves around the axons of neurons. Their PNS
counterpart, Schwann cells, are also considered glial cells. This sheath insulates the axon and
increases the speed of transmission, analogous to the coating on electrical wires. Microglia are
considered to be "immune system–like"; removing viruses, fungi, and other wastes that are present.
Astrocytes, however, are considered to be the most prominent. Their functions span throughout the
brain, including, but not limited to: the synchronization of axonal transmission via G–protein–
coupled receptors, blood flow regulation via the dilation of blood vessels, and the performance of
reactive gliosis in conjunction with microglia. Both astrocytes and oligodendrocytes develop from
neuroepithelial cells. Other types of glial cells include Radial glia, which direct immature neuron
migration during development.
Astrocytes have been shown to communicate amongst themselves, as well as participate in
bidirectional communication with neurons via the 'Tripartite synapse '. Ca2+–dependent glutamate
release also

The Serration Of Microglial Cells
Microglial expression and proliferation were previously well detected in various diabetes related
studies (Zeng et al., 2000; Daulhac et al., 2006; Li et al., 2011; Nagayach et al., 2014 a, b).
Similarly, our data showed an evident activation directed morphological transformation in
microglial cells, i.e., from resting to reactive phenotype consistent in both dorsal and ventral
hippocampal fields following diabetes. During 2nd and 4th week of diabetes the microglial cells are
in their intermediate activated state and from the 6th week onwards the presence of highly activated
hypertrophied microglial cells were clearly observed in OX–42 immunolabelling. Quantitative data
of both dorsal and ventral hippocampus also showed the marked ... Show more content on
Helpwriting.net ...
Hence, in the present study, the elevated expression of ED–2 in both dorsal and ventral
hippocampus accounts for the incidence of alternate activation of macrophages and microglia
activation up to the 12th week PDC. A recent study on AD has also shown that the ED–2 positive
cells were present in higher density around the compromised blood vessels (Pey et al., 2014) might
be indicating the BBB breakdown. This information supports the functional aspect of ED–2
expression in the resolution phase of inflammation (Polfliet et al., 2006) due to infiltration of
inflammatory molecules following BBB damage (Perry, 2004). In our previous study (Nagayach et
al., 2014a) we reported the astrocytic fragmentation a possible sign for the compromised functioning
of the blood brain barrier (Huber et al., 2006) and oxidative stress (Mastrocola et al., 2005) in the
brain following diabetes. Considerably, the recorded intense expression of ED–2 was might be a
consequence of BBB damage. In addition to this, it might also be possible that the observed intense
expression of ED–2 in the diabetic hippocampus (both dorsal and ventral) was aggravated by the
activated microglia to further facilitate its role in initiating the cascade of events of the immune
system. Similarly, the presence of ED–2

Gender Differences In Pain Essay
Gender differences in Pain
According to a recently published article (1) patients with knee osteoarthritis, women experienced
greater sensitivity to various pain modalities. The research conducted by a group of investigators
from the University of Florida in Gainesville and the University of Alabama at Birmingham, was
published Oct. 5 on the website of the journal Arthritis Care & Research.
In the study, there were 288 patients ages 45–85 underwent a series of assessments to measure their
sensitivity to contact heat, cold pressor, mechanical pressure and punctate stimulus. Result was,
compared to men, women showed lower tolerances for heat, cold and pressure and greater temporal
summation of pain. But, there were no differences by sex in ... Show more content on
Helpwriting.net ...
This could lead us to gender–based pain treatment. Between men and women, not all pain is equal.
Scientists have known this for quite some time now. Women are far more sensitive to pain than men.
They also suffer more from painful conditions, including migraines, arthritis, and fibromyalgia, and
their brains even process pain in different regions than men's. Why then, do women and men get the
same treatment for their pain? A group of researchers (5) recently searched how male and female
mice respond to pain, and found that it activated different types of immune cells. After injuring both
male and female mice's feet, the researchers tested pain sensitivity in both after administering a drug
that targeted immune cells known as microglia. These cells reside in the brain and spinal cord,
acting as a first line of defense in the central nervous system (CNS). Considering pain instantly
triggers an immune response in the CNS – one that persists in people with chronic pain – it would
make sense that the drug, which was meant to suppress the microglia, would reduce pain. However,
this only happened in the male mice. The researchers found that the females still experienced touch
sensitivity, a common symptom of chronic pain. Among the female mice, the researchers found a
different type of immune cell was likely responsible for responding to pain: T cells, a second line of
defense typically responsible for seeking out pathogens and killing them. For this reason, the
microglia–suppressing drug didn't

Biological Psychiatry
References
1. Spencer S, Xu L, Clarke M, Lemus M, Reichenbach A, Geenen B et al. Ghrelin Regulates the
Hypothalamic–Pituitary–Adrenal Axis and Restricts Anxiety After Acute Stress. Biological
Psychiatry. 2012;72(6):457–465.
In this article, Spencer et. al. observed the effect of the presence of endogenous Ghrelin on anxiety
behaviour in mice. This data was obtained by running wild type and Ghrelin knockout–mice through
a series of anxiety behaviour tests, as well as treating the knockout mice with exogenous Ghrelin
following these tests and running these again. The focus of the research was on the anxiety
behaviour displayed by the mice as well as the hypothalamic–pituitary–adrenal axis responses after
acute stress experiences of the mice ... Show more content on Helpwriting.net ...
The research focuses on observing the mice in a hippocampus–dependent spatial learning task, the
Active Place Avoidance Task, to show that adult–born immature neurons are necessary in order for a
subject to successfully obtain spatial learning. This article is useful to the research topic as the same
animal model is used for the observation of the importance of microglia on anxiety in rats. A
limitation of the study is that the results obtained during the spatial recall portion of the study were
not supported by previous studies on the role of immature neurons in the adult brain in spatial
memory recall, and should be further investigated. Overall, the authors observed that immature,
adult–born neurons are important in spatial task learning however, their presence does not appear to
have a significant effect on the recall ability of the subjects following their depletion. This article
does not form the basis of the research topic however, it is useful as the animal model created here is
that which the research methods will be modifying for use.
3. Lei Y, Chen C, Yan X, Li Z, Deng X. Early–life lipopolysaccharide exposure potentiates forebrain
expression of NLRP3 inflammasome proteins and anxiety–like behavior in adolescent rats. Brain
Research. 2017;1671:43–54.
In this paper, Lei et. Al. observed the effect of early life exposure to

Alzheimer's Disease Research Paper
Alzheimer's disease
Dementia is a broad category of brain diseases that cause long term loss of the ability to think and
reason clearly that is severe enough to affect a person's daily functioning. Alzheimer's disease (AD)
is the most common form of dementia. It primarily affects mainly older adults. Memory impairment
is an essential feature of AD.
Human central nervous system (CNS) is composed of neuron and glial cell ( astrocytes,
oligodendrocytes, microglia) which act as structural support of brain and also contribute for
formation of synapse. Microglia comprises 10% of the adult CNS. When there is tissue injury,
trauma or pathogen, ramified microglia will undergo biochemical changes and turned into an
activated microglia. The cell body ... Show more content on Helpwriting.net ...
The experiment model Include a hypertrophic heart rat (HHR) and a normal heart rat (NHR). The
HHR model showed no cardiac hypertrophy at maturity. Tissue from both HHR and NHR had been
extracted. The cardiac weight index (CWI) was collected. The cardiomyocyte were then obtained
via enzymatic procedure from both neonatal and adult NHR na HHR. Nuclei are then stained.
Polymerase chain reaction (PCR) were used to search mRNA expression levels of ANP,
BNP,MHC,p53, bax–1 and bcl–2 in ventricular tissues of HHR and NHR. Pl3K assay and western
blot analysis were then performed. Lastly, a statistical analysis with value P<0.05 was obtained. The
disadvantages of using this method were that the western blotting method is consider as a time
consuming process that also require high technical demand. However, the interaction between
antibodies and specific target protein can be clearly outlined. This will increase the sensitivity and
specificity in the mixtures that contain mixture of

Cytokines : Causes And Complications Of The Policiune System
Generally, the term cytokine describes the families of secreted proteins that regulate multiple
biological processes, including the innate and adaptive responses of the immune system (Steinke
2013, Sacca 2017, Dinarello 2000). They regulate these responses by performing a multitude of
important functions in the cells of the body, and lead to growth, differentiation and activation in
their targets (Steinke 2013). Each cytokine family fulfills one or many specific roles in the immune
system, for example the stimulation of lymphocyte growth or the promotion of inflammation
(Steinke 2013, Sacca 2017).
Pro–inflammatory cytokines are those which – among several other negative consequences –
promote inflammation and tissue destruction ... Show more content on Helpwriting.net ...
The cytokine is produced upon initiation of the inflammatory response (Gabay 2006). Here, IL–6
binds to the IL–6 receptor – which is composed of two subunits (Ni 2004). The α subunit of the IL–
6 receptor carries the glycoprotein gp130 – one of the primary signal–transducers involved in the
immune response, found on both the soluble and membrane–bound IL–6 receptors (Ni 2004,
Scheller 2014). The IL–6/IL–6R complex initiates a proteolytic cascade which proceeds to activate
the JAK2 kinases of the JAK/STAT signal transduction pathway (Ni 2004). The activated JAK2
kinases phosphorylate signal transducers and activators of transcription (STATs), which activates
transcription factors downstream (Rane 2000, Schindler 1995). The transcription factors pair to form
a dimer and subsequently migrate to the nucleus to activate the gene transcription (Ni 2004). As a
result, the proteolytic cascade initiated by the IL–6/IL–6R complex up–regulates inflammatory
mediators and innate immune responses and regulates the expression of genes involved in
inflammation, apoptosis, and oxidative stress (Erta 2012, Sacca 2017). Under normal conditions,
IL–6 is produced by macrophages, and in endothelial cells and T–cells in response to pathogen–
associated molecular patterns (PAMPs) and damage–associated molecular patterns (DAMPs)
(Abbas 2015, Dowalti 2010). It is therefore produced at the

Alzheimer 's Disease Detected By Alzheimer Mouse Models
Alzheimer's disease Detected in an Earlier Stage
The biological field is in constant investigation and there are new findings all the time. Science is so
exciting that writers, educators and publishers want to make it available and understandable to
everyone. Being this the case, people generate easy accessible websites with the intention to inspire
others to acquire knowledge of what's new in science, so they include the new findings, most of the
time from journal reports of PhD students or a team of researchers have done. An example of these
types of websites is "iflscience.com," where I found an article called "Destruction of Brain Cell
Connections May Be the Earliest Indicator of Alzheimer's" about a new discover that could help in
the ... Show more content on Helpwriting.net ...
The topics include: Alzheimer's disease and what provokes it, amyloid–beta proteins, synapses,
synaptic pruning, neurons, cognitive and microglial cells. Alzheimer's disease affects mostly
individuals in their mid–60s and is "a type of dementia that causes problems with memory, thinking
and behavior" (Alzheimer 's Association). The articles reflect the discovery of the Alzheimer's
disease affects the brain by the destruction of the connection of the brain cells which causes damage
in neurons and accelerate cognitive decline, and occasionally call it the earliest stage. Amyloid–beta
is a term that refers to the plaques made by the proteins which interferes and cause the loss of
synapses also known as synaptic pruning is the loss of connections between neurons caused
microglia, that according with The Campbell Biology In Focus textbook, "microglia are immune
cells that protect against pathogens" (Campbell.) The authors of the research support "microglia that
prune excess synapses in development are inappropriately activated and mediate synapse loss in
Alzheimer's disease." (Taub, 2016)
The prior terms explain what happen with the brain in that early stage, that after this research, it is
able to identify. The researchers describe in the journal article the use of C1q, "the initiating protein
of the classical complement cascade, is increased and associated with synapses before overt plaque
deposition" (Hong et al, 2016). Incorporation of

Essay On The Role Of NE In Ne
NE has also been shown to restrict pro–inflammatory processes {Feinstein, 1993 #19}, {Madrigal,
2006 #55}{Szabo, 1997 #84} and reduce neurotoxicity triggered by Aβ treatment in vitro
{Madrigal, 2007 #57}. It has been suggested that NE can protect neurons from the toxic effects of
Aβ by activating peroxisome proliferator activated receptors (PPAR) delta and increasing
glutathione production. This is based on the experiments in which the neuroprotective effects of NE
were partially blocked by co–treatment with an antagonist of PPARs, and replicated by incubation
with a selective PPARdelta agonist {Madrigal, 2007 #57}. Both NE and β2AR agonist–
isoprenaline, promote amyloid β peptide uptake and degradation by murine microglial through ...
Pro–inflammatory changes lead to significant impairment in cognitive function in mouse models of
AD {Heneka, 2002 #28}, {Heneka, 2006 #30}, {Jardanhazi–Kurutz, 2010 #38}, {Kalinin, 2007
#39} {Pugh, 2007 #69}. In addition, DSP4–mediated destruction of NE–ergic cells leads to
decreased migration and phagocytosis by microglia and reduced colocalization between microglia
and Aβ {Heneka, 2010 #29}. This suggests that a loss of NE–ergic cells could result in lower
microglial cell function and a decrease in Aβ clearance in patients with AD. Indeed, DSP–4
injections in the Ts65Dn mouse model of DS has resulted in increased hippocampal inflammation
and accelerated degeneration into AD–like pathology {Lockrow, 2011 #54}. NE deficiency induced
by DSP–4 injections lead to a disruption in the neural–glial interactions and increased inflammatory
signaling {Braun, 2014 #9}. For instance, adult rats injected with DSP–4 followed by Aβ injection
showed increase in inflammatory markers including iNOS, IL–1B, and IL–6. When Aβ was injected
alone into the mice, iNOS was expressed primarily in the microglia, but injection of both Aβ and
DSP–4 resulted in iNOS expression in neurons {Heneka, 2002 #28}. As expected, increased NE
levels can attenuate this effect. Based on this, it appears that the loss of NE is driving this cascade of
events {Heneka, 2002 #28}. It has already been shown that NE agonists can

Multiple System Atrophy : An Adult Onset Progressive...
Multiple System Atrophy (MSA) is an adult onset progressive neurodegenerative disease,
characterized by various degrees of Parkinsonism, cerebellar ataxia, and failure of the autonomic
nervous system. MSA is classified as a α–synucleinopathy, a subset of neurodegenerative diseases
characterized by the accumulation of misfolded α–synuclein (α–Syn) in the CNS (Fellner et al.,
2011; MartÌ et al., 2003). In MSA, α–syn aggregates appear primarily as glial cytoplasmic
inclusions (GCIs) in oligodendrocytes (Wakabayashi et al., 1998). The accumulation of α–syn
aggregates is associated with glial pathology and neuroinflammation in MSA and other α–
synucleinopathies such as, Parkinson's disease (PD) and dementia with Lewy bodies (DLB) (Fellner
et al., 2011). Microglia activation has also been implicated in α–synucleinopathies as well as other
neurodegenerative disorders including Alzheimer's disease (AD) and Multiple Sclerosis (MS)
(Fellner et al. 2011; Minagar et al., 2002). To further define immune activity in MSA,
immunohistochemistry (IHC) was performed on sections of human pons tissue to determine changes
in expression of specific immune proteins in MSA versus control tissues. While other studies have
investigated the role of immune proteins in various brain regions of MSA patients (Ishizawa et al.,
2004; Stefanova et al., 2007), our study focused on the pontocerebellar fiber tracts, a region in MSA
containing a large number of GCIs. We hypothesized that increased presence of

Inflammation In Central Nervous System Essay
Inflammation in the central nervous system (CNS) is particular, as the cells that intervene during
this process are specific of this system: the glial cells. Glial cells are non–neuronal cells that
maintain homeostasis, form myelin, and provide support for neurons in the CNS and peripheral
nervous system13.
Astroglial cells are star–shaped glial cells that are especially important for the repair and scarring
process in traumatic injuries, and for the formation of the blood–brain barrier (BBB). Although the
BBB is able to protect the CNS from peripheral immune activation, it becomes more permeable
during inflammation, which renders the brain vulnerable to infections; so a closer look is given to
the BBB in inflammation and immunity in some research projects14. Under physiological
conditions, astrocytes maintain the extracellular homeostasis, participating in glutamate uptake and
its ... Show more content on Helpwriting.net ...
Since antibodies are not normally present in the CNS, microglial cells are the main active immune
defense. As they are extremely plastic, microglia can adopt different morphologies, which two of the
most important are the ramified and the activated one. The highly ramified morphology corresponds
to the "resting" microglia, with long branches constantly moving and a small cellular body. The
activated microglia presents a small amoeboid cell body with thicker and retracted branches, and it
is associated with a pro–inflammatory phenotype. Microglial cells can go through the classical
activation by stimulation with LPS and IFN–γ and can produce pro–inflammatory
cytokines/mediators such as IL–1β, IL–6, TNF–α, CCL2, ROS, and NO18,19; suggesting that these
molecules contribute to dysfunction of neural network in the CNS20. The microglia in this state is
termed "M1 microglia", while "M2 microglia" is used to include the states of both alternative
activation21. IL–4 and IL–13 can induce alternative activation,

Glial Activation And Proinflammatory Cytokines In APP /...
12. Zhu 2014 Quetiapine attenuates glial activation and proinflammatory cytokines in APP/PS1
transgenic mice via inhibition of nuclear factor–κB pathway.
Abstract
Background:
In Alzheimer's disease, growing evidence has shown that uncontrolled glial activation and
neuroinflammation may contribute independently to neurodegeneration. Antiinflammatory strategies
might provide benefits for this devastating disease. The aims of the present study are to address the
issue of whether glial activation and proinflammatory cytokine increases could be modulated by
quetiapine in vivo and in vitro and to explore the underlying mechanism.
Methods:
Four–month–old amyloid precursor protein (APP) and presenilin 1 (PS1) transgenic and
nontransgenic mice were ... Show more content on Helpwriting.net ...
devastating disease.
In the central nervous system, microglia and astrocytes are the major type of glial cells, and
activation of these cells has been involved in all neurodegenerative diseases (Wyss–Coray and
Mucke, 2002). Nevertheless, the diverse physiological functions of glial activation might complicate
the interpretation of experimental

A Role for Hippocampal Neurogenesis in Learning and Memory...
Inflammatory modulation of learning and memory– A role for hippocampal neurogenesis?
Hippocampal neurogenesis
Neurogenesis is the birth of new neurons. It is a multistep process which consists of asymmetric
division of neural stems ultimately leading to the generation of new neurons. In the hippocampus,
neurogenesis occurs predominantly during embryonic development and also during adulthood
(Altman and Das, 1965). In the human brain, adult neurogenesis occurs in the subgranular zone of
the dentate gyrus throughout life (Eriksson et al., 1998). Newly formed cells in the subgranular layer
then migrate to the granular layer of the dentate gyrus where they express a neuronal phenotype
(Kuhn et al., 1996). These adult–formed granule cells are ... Show more content on Helpwriting.net
...
The mice were placed in an open–field square which had a striped pattern on one wall of the field.
Two identical objects were placed in the field. The test consisted of an exploration phase and a test
phase. During the exploration phase the MAM treated mice as well as the control mice spent the
same amount of time exploring the objects. However during the test phase, in which one object was
moved to a new location, the MAM treated mice spent a significantly less amount of time exploring
the object in the new location in comparison to the control mice. This suggests that the MAM
treated mice were unable to discriminate between the novel and familiar location (Goodman et al.,
2010).
The Morris Water Maze (MWM) is a behavioural test that can test the hippocampal dependent
spatial learning ability of rodents. Rodents with hippocampal lesions show impaired performance in
this test (Morris et al., 1982). Evidence suggests that neurogenesis is involved in long term spatial
memory of rodents. Rats were subjected to whole brain irradiation to eliminate adult neurogenesis.
Rats were placed in a circular pool of water with a submerged platform in one of its quadrants. The
platform was not visible due to the water being opaque. There were spatial cues around the circular
pool that could be used as cues to learn the spatial location of the platform. The

The Incidence Of Alzheimer 's Disease Essay
Etiology
The incidence of Alzheimer's disease is 36 million people worldwide as of 2010, making it the most
common cause of senile dementia. 1This number is expected to nearly double, to 65.7 million by
2030.1AD is accompanied by pathological features consistent with brain atrophy and neural cell
death. 1The inflammatory response of the brain, that is commonly found in AD, is linked to several
factors. 1Amyloid–B, inflammatory cytokines, and sphingolipids are some of the known factors
associated with AD. 1Uncontrolled inflammation, from ongoing or chronic complement activation is
theorized to impact Alzheimer's disease, among other diseases. 2 Recent GWAS shows strong
evidence that complement receptor CR1 is linked to the development of AD, although the
mechanistic basis for the CR1 risk remains largely unknown.2
Pathogenesis
Emerging evidence demonstrates neuroinflammation as a crucial pathophysiology of AD,
specifically impacted by microglia and astroglia. 3 The microglia are distributed evenly across the
brain and are activated by protein aggregation and neuronal cell death. 3 Specifically related to AD,
the two chief proteins involved are amyloid–B and tau.3 An accumulation of microglia around
amyloid–B plaques has been documented in post–mortem human brains and in animal models with
AD.3 Research has yet to clearly determine if microglial activation plays a beneficial or detrimental
role in the progression of AD..3 Some reports suggest that microglia are attracted to

Glial Activation And Proinflammatory Cytokine In...
Int J Neuropsychopharmacol. 2014 Oct 31;18(3). pii: pyu022. doi: 10.1093/ijnp/pyu022. Quetiapine
attenuates glial activation and proinflammatory cytokines in APP/PS1 transgenic mice via inhibition
of nuclear factor–κB pathway. Zhu S1, Shi R1, Li V1, Wang J1, Zhang R1, Tempier A1, He J1,
Kong J1, Wang JF1, Li XM2. Author information Abstract BACKGROUND: In Alzheimer's
disease, growing evidence has shown that uncontrolled glial activation and neuroinflammation may
contribute independently to neurodegeneration. Antiinflammatory strategies might provide benefits
for this devastating disease. The aims of the present study are to address the issue of whether glial
activation and proinflammatory cytokine increases could be modulated by quetiapine ... Show more
devastating disease. In the central nervous system, microglia and astrocytes are the major type of
glial cells, and activation of these cells has been involved in all neurodegenerative diseases (Wyss–
Coray and Mucke, 2002). Nevertheless, the

Gene And Microglia Mediate Early Synapse Loss Essay
In the primary research article given to us titled "Complement and microglia mediate early synapse
loss in Alzheimer mouse models" it talks about a study about the causes of Alzheimer's disease in
mice. Alzheimer's is believed to be caused by multiple factors. One of these are called complement
proteins. According to the University of Washington, they are a group of around 20 different
proteins that assist with fighting infections. Complement proteins are found in our blood and they
assist in fighting infections in various ways. Some of these proteins bind to the surface of a pathogen
were antibodies are already present to make sure that the pathogen is phagocytized. Other proteins
cause histamines to be released or act as a signal to draw phagocytes to the pathogens. According to
the National Center for Biotechnology Information, C3 is a type of complement protein that is vital
to the activation of the entire complement system. C1q is another complement protein that it is a
piece of the classical pathway for the activation of the complement system. According to the The
Green Lab at the University of California Irvine, macroglia are the immune cells of the central
nervous system. Their functions include removing bacteria and unwanted materials from the brain.
In order to combat neurological damage and inflammations they have to be activated first.
According to the Alzheimer 's Association, Alzheimer's is a disease that causes a steady decline in
brain functions such as

Microglia Essay
Microglia
Microglia serve as the resident innate immune cells of the brain parenchyma which play different
roles in adult and developing CNS ranging from immunological surveillance to neurological
preservation.17,18 Although microglia are the primary cells involved in innate immunity in the
CNS, astrocytes and neurons also take part in immune response.19 Microglia were firstly identified
as rod–shaped nucleus containing cells in the brain over one–hundred years ago and were named
Staebchenzellen.20 Microglia with the capacity for self–renewal and long–living originate from
myeloid progenitors within the yolk sac and migrate to the developing CNS during early
embryogenesis. They are different from the cells derived from the bone marrow by haematopoiesis
and from the blood circulating cells.21,22 These phagocytes make up approximately 10% of
heterogeneous cell population in CNS and trigger both innate and adaptive immunities in
neuroinflammation.12,13 ... Show more content on Helpwriting.net ...
Conversely, alternative activated microphages typically protect the body from disorders.22 In other
words, macrophages can be detrimental and participate in the progression of numerous
neuroinflammatory diseases.28 C–type lectin receptor of macrophages plays a vital role in
neuroinflammation by recognizing the ligands generated by necrotic cells and secreting pro–
inflammatory mediators like interleukin–1β (IL–1β), tumor necrosis factor–α (TNF–α) and NO
following stroke and other neurological

Traumatic Brain Inflammation

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