Regeneration of Brain with new understanding gives us good ground to be optimistic in matters of research and also day to day clinics. This presentation at the most introduces you to the potential stride of the field.

1. REGENERATION OF MIND AND BRAIN
Devashish konar MD Consultant Psychiatrist
Mental Health Care Centre, Kolkata and Burdwan
M: +91 9434009113
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2. THE MIND BOGGLING COMPLEXITIES OF THE MASTER ORGAN
BRAIN
• The human nervous system is the organ of consciousness, cognition,
ethics, and behavior; as such, it is the most intricate structure known to
exist.
• More than one-third of the 23,000 genes encoded in the human genome
are expressed in the nervous system.
• Each mature brain is composed of 100 billion neurons, several million
miles of axons and dendrites, and >1015 synapses.
• Neurons exist within a dense parenchyma of multifunctional glial cells
that synthesize myelin, preserve homeostasis, and regulate immune
responses.
• Measured against this background of complexity, the achievements of
molecular neuroscience have been extraordinary.
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3. ACHIEVEMENTS ARE COMMENDABLE AND TASKS ARE GIGANTIC
• In spite of better understanding of brain physiology in the last 25 years,
the fact remains that psychiatric illnesses are on increase and we have
not made any strong headway in preventing these illnesses.
• All serious psychiatric illnesses from depression to schizophrenia to
dementia have neuronal degeneration in different areas of brain.
• Increased levels in oxidative stress, mitochondrial dysfunction,
excitotoxicity, inflammatory changes, iron accumulation, and protein
aggregation are some of the common ways in which neuronal
degeneration occurs.
• For neuroprotective treatment you need to focus on these pathologies.
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4. REGENERATION OF BRAIN AND MIND: MAJOR THRUST
AREA OF FUTURE NEUROSCIENCES
• With new methods in basic neuroscience we have improved our
understanding of neurodegeneration and regeneration.
• Natural methods, like life style changes and drugs which can alter the
health of neuronal tissue have been worked upon and some
important clues have been found.
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5. THE ACUMULATING CLUES TO OUR UNDERSTANDING
• Glutamate receptors, specifically N-Methyl-D-Aspartate (NMDA) receptors
• Glutamate antagonists
• Antioxidants
• Brain-derived neurotrophic factor (BDNF) and other neurotrophin family of
growth factors
• Insulin receptors are the latest to have increased our understanding of
molecular psychiatry
As more data accumulate time will be ripe to translate these
understanding into bedside wisdom
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6. FUNCTIONS OF NEUROTROPHIC FACTORS
Neurotrophic factors are secreted proteins that modulate neuronal
growth, differentiation, repair, and survival; some have additional
functions, including roles in neurotransmission and in the synaptic
reorganization involved in learning and memory.
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7. 7
TNeurotrophin family
Nerve growth factor
Brain-derived neurotrophic factor
Neurotrophin-3
Neurotrophin-4
Neurotrophin-6
Cytokine family
Ciliary neurotrophic factor
Leukemia inhibitory factor
Interleukin 6
Cardiotrophin-1
Transforming growth factor β family
Glial-derived neurotrophic family
Neurturin
Persephin
Fibroblast growth factor family
Hepatocyte growth factor
Insulin-like growth factor (IGF) family
IGF-1
IGF-2
NEUROTROPHIC FACTORS

8. CONTRARY TO CONVENTIONAL THOUGHT AS EXPRESSED IN THIS
DIAGRAM, BRAIN FUNCTIONS ARE NOT CONFINED TO CERTAIN
FIXED LOCATIONS
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9. NEUROPLASTICITY
• Neuroplasticity, also known as brain plasticity, is an umbrella
term that describes lasting change to the brain throughout an
animal's life course.
• The term gained prominence in the later half of the 20th
century, when new research showed many aspects of the brain
remain changeable (or "plastic") even into adulthood.
• This notion contrasts with the previous scientific consensus
that the brain develops during a critical period in early
childhood, then remains relatively unchangeable (or "static")
afterward.
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10. NEUROPLASTICITY
• Neuroscientists distinguish synaptic plasticity, which refers to changes in
how neurons connect to each other, from non-synaptic plasticity, which
refers to changes in the neurons themselves.
• One of the fundamental principles of how neuroplasticity functions is
linked to the concept of synaptic pruning, the idea that individual
connections within the brain are constantly being removed or recreated,
largely dependent upon how they are used.
• This concept is captured in the aphorism, "neurons that fire together, wire
together"/"neurons that fire apart, wire apart," summarizing Hebbian
theory.
• If there are two nearby neurons that often produce an impulse
simultaneously, their cortical maps may become one.
• This idea also works in the opposite way, i.e. that neurons which do not
regularly produce simultaneous impulses will form different maps.
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11. I WILL GIVE YOU FOUR EXAMPLES
• Human echolocation in visually impaired
• Learning difficulty
• ADHD
• Phantom limbs
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12. HUMAN ECHO-LOCATION
• Human Eco-location is a learned ability for humans to sense
their environment from echoes. This ability is used by some
blind people to navigate their environment and sense their
surroundings in detail.
• Studies in 2010 and 2011 using functional magnetic resonance
imaging techniques have shown that parts of the brain
associated with visual processing are adapted for the new skill
of echolocation.
• Studies with blind patients, for example, suggest that the click-
echoes heard by these patients were processed by brain regions
devoted to vision rather than audition.
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13. LEARNING DIFFICULTY
• Michael Merzenich developed a series of plasticity-based computer
programs known as Fast Forword.
• FastForWord offers seven brain exercises to help with the language and
learning deficits of dyslexia.
• In a recent study, experimental training was done in adults to see if it
would help to counteract the negative plasticity that results from age-
related cognitive decline (ARCD).
• The experimental training design included six exercises designed to
reverse the dysfunctions caused by ARCD in cognition, memory, motor
control, and so on.
• After use of the experimental training program for 8–10 weeks, there was
a significant increase in task-specific performance.
• The data collected from the study indicated that a neuroplasticity-based
program could notably improve cognitive function and memory in adults
with ARCD.
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14. ADHD
Reviews of magnetic resonance imaging (MRI) studies suggest that the
long-term treatment of attention deficit hyperactivity disorder (ADHD)
with stimulants, such as amphetamine or methylphenidate, decreases
abnormalities in brain structure and function found in subjects with
ADHD, and improves function in several parts of the brain, such as the
right caudate nucleus of the basal ganglia.
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15. PHANTOM LIMBS
• The experience of Phantom limbs is a phenomenon in which a person
continues to feel pain or sensation within a part of their body which
has been amputated.
• This is strangely quite common, occurring in 60–80% of amputees.
• An explanation for this refers to the concept of neuroplasticity, as the
cortical maps of the removed limbs are believed to have become
engaged with the area around them in the postcentral gyrus.
• This results in activity within the surrounding area of the cortex being
misinterpreted by the area of the cortex formerly responsible for the
amputated limb.
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16. PHANTOM LIMBS
• The relationship between phantom limbs and neuroplasticity is a complex one.
• In the early 1990s V.S. Ramachandran theorized that phantom limbs were the
result of cortical remapping.
• In 1995 Herta Flor and her colleagues demonstrated that cortical remapping
occurs only in patients who have phantom pain.
• Her research showed that phantom limb pain (rather than referred sensations)
was the perceptual correlate of cortical reorganization.
• This phenomenon is sometimes referred to as maladaptive plasticity.
• With treatment, pain relief is possible in many, though not always.
Findings extend our understanding of the brain's plasticity because there is
evidence that profound changes in the mental representation of the body can be
induced purely by internal brain mechanisms—the brain truly does change itself. 16

17. NEUROGENESIS, MIGRATION AND CELL REPLACEMENT
• From clinical and therapeutic perspectives, fundamental questions
are whether changes in neurogenesis contribute to disease and
whether newly formed neurons undergo migration to and integration
into regions of injury, replacing dead cells and leading to functional
recovery.
• A neurogenetic response has now been shown for multiple
conditions in the adult, including brain trauma, stroke, and epilepsy.
• For instance, ischemic stroke in the striatum stimulates adjacent
subventricular zone (SVZ) neurogenesis with neurons migrating to the
injury site.
• Furthermore, in a highly selective paradigm not involving local tissue
damage, degeneration of layer 3 cortical neurons elicited
subventricular zone (SVZ) neurogenesis and cell replacement.
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18. NEUROGENESIS: THE OTHER IMPLICATIONS
• These studies raise the possibility that newly produced neurons
normally participate in recovery and may be stimulated as a
novel therapeutic strategy.
• However, in contrast to potential reconstructive functions,
neurogenesis may also play role in pathogenesis: in a kindling
model of epilepsy, newly generated neurons were found to
migrate to incorrect positions and participate in aberrant
neuronal circuits, thereby reinforcing the epileptic state.
• Conversely, reductions in neurogenesis may contribute to several
conditions that implicates dysfunction or degeneration of the
hippocampal formation.
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19. EXITOTOXICITY
• Dentate gyrus neurogenesis is inhibited by increased glucocorticoid
levels observed in aged rats and can be reversed by steroid
antagonists and adrenalectomy, observations potentially relevant to
the correlation of elevated human cortisol levels with reduced
hippocampal volumes and the presence of memory deficits.
• Similarly, stress-induces increases in human glucocorticoids may
contribute to decreased hippocampal volumes seen in schizophrenia,
depression, and posttraumatic stress disorder.
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20. THE IMPORTANCE OF GLIA IN DEALING WITH STRESS
• Glia are starting to be accepted as the equal of neurons.
• Glia has role in stress and disease.
• Many glial modulators have been worked upon.
• Environmental enrichment and exercise can increase intelligence, a
buffer against stress, most likely via glial involvement.
• Cerebral dominance is also related to how glia respond to stress
resulting in psychiatric illness.
• Glial effects on depression and schizophrenia have been observed.
• Astrocytes, microglia, NG2 (Polydendrocytes) cells, and
oligodendrocytes all contribute.
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21. MICROGLIA ACROSS ROLES
• Suicidal ideation can increase the permeability of the BBB resulting in
the increase in serum levels of a glial protein S100B that has become
a marker for the intensity of suicidal risk.
• Microglia form one of the bases of the inflammatory theory of
psychiatric disorders.
• Minocycline, adenosine and cAMP inhibitors, such as PDE-4
inhibitors, have been used to modulate the microglia, with positive
results in psychiatric illness.
• Controlling the microglia can even be protective against drug abuse.
• Recently a “glymphatic” system has been discovered in mice that if
applicable to humans means that we clean out our brain in sleep.
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22. PLASTICITY IN ADULTHOOD
• By the time we’re twenty-five years of age, the brain transformations of
childhood and adolescence are to a great extent over.
• The tectonic shifts in our identity and personality have ended, and our brain
appears to now be fully developed.
• There is no need to think that who we are as adults is now fixed in place,
immoveable.
• Even in adulthood: experience changes our brain, and it retains the change.
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23. A GOOD EXAMPLE: CAB DRIVERS OF LONDON
• They undergo four years of intensive training to pass the
“Knowledge of London”.
• The knowledge requires aspiring cabbies to memorize London’s
extensive roadways, in all their combinations and permutations.
• This is an exceedingly difficult task: the knowledge covers 320
different routes through the city, 25,000 individual streets, and
20,000 landmarks and points of interest –hotels, theatres,
restaurants, embassies, police stations, sports facilities, and
anywhere a passenger is likely to want to go.
• Students of The knowledge typically spend three to four hours a day
reciting theoretical journeys.
• After learning the knowledge, the hippocampuses of London cab
drivers visible changed shape reflecting their improved skills of
spatial navigation. 23

24. STEM CELLS AND TRANSPLANTATION
• The nervous system is traditionally considered to be a
nonmitotic organ, in particular with respect to neurons.
• These concepts have been challenged by the finding that
neural progenitor or stem cells exist in the adult CNS that
are capable of differentiation, migration over long
distances, and extensive axonal arborization and synapse
formation with appropriate targets.
• These capabilities also indicate that the repertoire of
factors required for growth, survival, differentiation, and
migration of these cells exists in the mature nervous
system.
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25. BRAIN RESEARCH THROUGH ADVANCING INNOVATIVE
NEUROTECHNOLOGIES (BRAIN) INITIATIVE
• The BRAIN initiative, grand in scope, was launched in 2013 to speed
development of advances to understand, treat, repair, and prevent common
neurologic disorders that, in aggregate, affect more than 1 billion people
worldwide.
• The initial goal of BRAIN is to bring together experts in neurobiology
(including optogenetics), engineering, information technology, and other
fields to develop novel visualization and electrophysiologic methods to better
define and understand neural circuits and all the connections among
individual neurons.
• The announcement of the BRAIN initiative followed just weeks after a
similarly ambitious program, the Human Brain Project (HBP), was unveiled by
the European Union.
• The HBP seeks to model individual neurons, neural circuits, and ultimately
the entire brain using computer technologies.
• These two ambitious projects are expected to be complementary and over
time will hopefully become increasingly integrated.
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26. DAY TO DAY TIPS FOR HEALTHY BRAIN AND MIND
• An active life fuels an active brain
• Healthy food, plenty of water
• Socialisation
• Intellectual activities
• Switching hand is a good exercise
• Exercise, specially, walking and
breathing
• Travel and novel experience
• Challenge your brain always
• Meditation
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27. THE BRAIN BENEFITS OF REGULAR
EXERCISE
• Enhances blood flow
• Exercise may help slow brain shrinkage
in adults with Alzheimer’s.
• Regular exercise can help children
improve memory.
• Reduce gray-matter loss
• Improves concentration and attention
• Changes gene patterns
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28. THE APHORISM: PRACTICE MAKES A MAN PERFECT
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THE BRAIN IS LIKE A FOREST
WITH TRAINING THE BRAIN
BECOMES LIKE A SMART CITY

30. THANK
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