Pinel basics ch08

Chapter 8 Brain Damage and Neuroplasticity Can the Brain Recover from Damage?
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Causes of Brain Damage
Brain tumors
Cerebrovascular disorders
Closed-head injuries
Infections of the brain
Neurotoxins
Genetic factors

Brain Tumors
A tumor (neoplasm) is a mass of cells that grows independently of the rest of the body – a cancer
~20% of brain tumors are meningiomas – encased in meninges
Encapsulated, growing within their own membranes
Usually benign, surgically removable

Brain Tumors
Most brain tumors are infiltrating
Grow diffusely through surrounding tissue
Malignant, difficult to remove or destroy
About 10% of brain tumors are metastatic – they originate elsewhere, usually the lungs

Cerebrovascular Disorders
Stroke – a sudden-onset cerebrovascular event that causes brain damage
Cerebral hemorrhage – bleeding in the brain
Cerebral ischemia – disruption of blood supply
3 rd leading cause of death in the US and most common cause of adult disability

Cerebrovascular Disorders
Cerebral hemorrhage – blood vessel ruptures
Aneurysm – weakened point in a blood vessel that makes a stroke more likely. Congenital or due to poison or infection.
Congenital – present at birth
Cerebral ischemia – disruption of blood supply
Thrombosis – plug forms
Embolism – plug forms elsewhere and moves to the brain
Arteriosclerosis – wall of blood vessels thicken, usually due to fat deposits

Damage due to Cerebral Ischemia
Does not develop immediately
Most damage is a consequence of excess neurotransmitter release – especially glutamate
Blood-deprived neurons become overactive and release glutamate
Glutamate overactivates its receptors, especially NMDA receptors leading to an influx of sodium and calcium ions

Damage due to Cerebral Ischemia
Influx of sodium and calcium triggers:
the release of still more glutamate
a sequence of internal reactions that ultimately kill the neuron
Ischemia-induced brain damage
takes time
does not occur equally in all parts of the brain
mechanisms of damage vary with the brain structure affected

Closed-Head Injuries
Brain injuries due to blows that do not penetrate the skull – the brain collides with the skull
Contrecoup injuries – contusions are often on the side of the brain opposite to the blow
Contusions – closed-head injuries that involve damage to the cerebral circulatory system. A hematoma, a bruise, forms.
Concussion – when there is a disturbance of consciousness following a blow to the head and no evidence of structural damage.

Concussions
While there is no apparent brain damage with a single concussion, multiple concussions may result in a dementia referred to as “punch-drunk syndrome”
When might this occur?
Can it be prevented?

Brain Infection
Invasion of the brain by microorganisms
Encephalitis – the resulting inflammation
Bacterial infections
Often leads to abscesses, pockets of pus
May inflame meninges, creating meningitis
Treat with penicillin and other antibiotics
Viral infections
Some viral infections preferentially attack neural tissues

Brain Infections - Some Causes
Bacterial
Syphilis – may produce a syndrome of insanity and dementia known as general paresis
Syphilis bacteria are passed to the noninfected and enter a dormant stage for many years.
Viral
Rabies – high affinity for the nervous system
Mumps and herpes – typically attack tissues other than the brain
Viruses may lie dormant for years

Neurotoxins
May enter general circulation from the GI tract, lungs, or through the skin
Toxic psychosis – chronic insanity produced by a neurotoxin.
The Mad Hatter – may have had toxic psychosis due to mercury exposure

Neurotoxins
Some antipsychotic drugs produce a motor disorder caused tardive dyskinesia
Recreational drugs, such as alcohol, may cause brain damage
Some neurotoxins are endogenous – produced by the body

Genetic Factors
Most neuropsychological diseases of genetic origin are associated with recessive genes. Why?
Down syndrome
0.15% of births, probability increases with advancing maternal age
Extra chromosome 21
Characteristic disfigurement, mental retardation, other health problems

Programmed Cell Death
Apoptosis – cell suicide – involved in all forms of brain damage discussed thus far
Apoptosis is adaptive, while necrosis involves inflammation and may lead to the damage of surrounding cells

Neuropsychological Diseases
Epilepsy
Parkinson’s disease
Huntington’s disease
Multiple sclerosis
Alzheimer’s disease

Epilepsy
Primary symptom is seizures, but not all who have seizures have epilepsy
Epileptics have seizures generated by their own brain dysfunction
Affects about 1% of the population
Difficult to diagnose due to the diversity and complexity of epileptic seizures

Epilepsy
Types of seizures
Convulsions – motor seizures
Some are merely subtle changes of thought, mood, or behavior
Causes
Brain damage
Genes – over 70 known so far
Diagnosis
EEG – Electroencephalogram
Seizures associated with high amplitude spikes

Epilepsy
Seizures often preceded by an aura, such as a smell, hallucination, or feeling
Aura’s nature suggests the epileptic focus
Warns epileptic of an impending seizure
Partial epilepsy – does not involve the whole brain
Generalized epilepsy – involve the entire brain

Partial Seizures
Simple
symptoms are primarily sensory or motor or both (Jacksonian seizures)
symptoms spread as epileptic discharge spreads
Complex – often restricted to the temporal lobes (temporal lobe epilepsy)
patient engages in compulsive and repetitive simple behaviors – automatisms
more complex behaviors seem normal

Generalized Seizures
Grand mal
Loss of consciousness and equilibrium
Tonic-clonic convulsions
-rigidity (tonus) and tremors (clonus)
Resulting hypoxia may cause brain damage
Petit mal
not associated with convulsions
A disruption of consciousness associated with a cessation of ongoing behavior

Parkinson’s Disease
A movement disorder of middle and old age affecting ~ .5%of the population
Pain and depression commonly seen before the full disorder develops
Tremor at rest is the most common symptom of the full-blown disorder
Dementia is not typically seen
No single cause

Parkinson’s Disease
Associated with degeneration of the substantia nigra whose neurons use dopamine
Almost no dopamine in the substantia nigra of Parkinson’s patients
Treated temporarily with L-dopa
Linked to ~10 different gene mutations

Huntington’s Disease
Also a progressive motor disorder of middle and old age – but rare, with a strong genetic basis, and associated with dementia.
Begins with fidgetiness and progresses to jerky movements of entire limbs and sever dementia
Death usually occurs within 15 years
Caused by a single dominant gene
1 st symptoms usually not seen until age 40

Multiple Sclerosis
A progressive disease that attacks CNS myelin, leaving areas of hard scar tissue (sclerosis)
Nature and severity of deficits vary with the nature, size, and position of sclerotic lesions
Periods of remission are common
Symptoms include visual disturbances, muscle weakness, numbness, tremor, and loss of motor coordination (ataxia)

Multiple Sclerosis
Epidemiological studies find that incidence of MS is increased in those who spend childhood in a cool climate
MS is rare amongst Africans and Asians
Strong genetic predisposition and many genes involved
An autoimmune disorder – immune system attacks myelin
Drugs may retard progression or block some symptoms

Alzheimer’s Disease
Most common cause of dementia – likelihood of developing it increases with age
Progressive, with early stages characterized by confusion and a selective decline in memory
Definitive diagnosis only at autopsy – must observe neurofibrillary tangles and amyloid plaques

Familial Forms of Alzheimer’s Disease
Several genes identified as involved in early onset AD
All affected genes are involved in synthesis of amyloid or tau, a protein found in the tangles
Not clear what comes 1 st – amyloid plaques or neurofibrillary tangles
Declined acetylcholine levels is among one of the earliest changes seen

Neuropsychological Diseases - Recap
Epilepsy – abnormal electrical activity
Parkinson’s disease
progressive motor disorder without dementia
Huntington’s disease
progressive motor disorder with dementia
Multiple sclerosis
autoimmune disorder that affects motor function and strikes early
Alzheimer’s disease - dementia

What Is an Animal Model?
A condition in a nonhuman animal that is similar in some respects to a human disease
While animal models only model some aspects of the human condition, they can provide insight
There are animal models of all five of the neuropsychological disorders discussed

MPTP Model of Parkinson’s Disease (PD)
The Case of the Frozen Addicts
Synthetic heroin produced the symptoms of Parkinson’s
Contained MPTP
MPTP and its metabolites cause cell loss in the substantia nigra, like that seen in PD
Animal studies led to the finding that deprenyl can retard the progression of PD

Neuroplastic Responses to Nervous System Damage
Degeneration - deterioration
Regeneration – regrowth of damaged neurons
Reorganization
Recovery

Degeneration
Cutting axons is a common way to study responses to neuronal damage
Anterograde - degeneration of the distal segment – between the cut and synaptic terminal
cut off from cell’s metabolic center
swells and breaks off within a few days
Retrograde – degeneration of the proximal segment – between the cut and cell body
progresses slowly
if regenerating axon makes a new synaptic contact, the neuron may survive

Neural Regeneration
Does not proceed successfully in mammals and other higher vertebrates - capacity for accurate axonal growth is lost in maturity
Regeneration is virtually nonexistent in the CNS of adult mammals and unlikely, but possible, in the PNS

Neural Regeneration in the PNS
If the original Schwann cell myelin sheath is intact, regenerating axons may grow through them to their original targets
If the nerve is severed and the ends are separated, they may grow into incorrect sheaths
If ends are widely separated, no meaningful regeneration will occur

Neural regeneration

Why do mammalian PNS neurons regenerate?
CNS neurons can regenerate if transplanted into the PNS, while PNS neurons won’t regenerate in the CNS
Schwann cells promote regeneration
Neurotrophic factors stimulate growth
CAMs provide a pathway
Oligodendroglia actively block regeneration

Neural Reorganization
Reorganization of 1° sensory and motor systems has been observed following damage to:
peripheral nerves
primary cortical areas
Lesion one retina and remove the other – V1 neurons that originally responded to lesioned area now responded to an adjacent area – remapping occurred within minutes
Studies show scale of reorganization possible is far greater than anyone assumed possible

How/why does damage lead to reorganization?
Strengthened existing connections due to a release from inhibition?
Consistent with speed and localized nature of reorganization
Establishment of new connections?
Magnitude can be too great to be explained by changes in existing connections

Recovery of Function after Brain Damage
Difficult to conduct controlled experiments on populations of brain-damaged patients
Can’t distinguish between true recovery and compensatory changes
Cognitive reserve – education and intelligence – thought to play an important role in recovery of function – may permit cognitive tasks to be accomplished new ways
Adult neurogenesis may play a role in recovery

Treating Nervous System Damage
Reducing brain damage by blocking neurodegeneration
Promoting recovery by promoting regeneration
Promoting recovery by transplantation
Promoting recovery by rehabilitative training

Reducing brain damage by blocking neurodegeneration
Various neurochemicals can block or limit neurodegeneration
Apoptosis inhibitor protein – introduced in rats via a virus
Nerve growth factor – blocks degeneration of damaged neurons
Estrogens – limit or delay neuron death
Neuroprotective molecules tend to also promote regeneration

Promoting Recovery by Promoting Regeneration
While regeneration does not normally occur in the CNS, experimentally it can be induced
Eliminate inhibition of oligodendroglia and regeneration can occur
Provide Schwann cells to direct growth

Promoting Recovery by Neurotransplantation
Fetal tissue
Fetal substantia nigra cells used to treat MPTP-treated monkeys (PD model)
Treatment was successful
Limited success with humans
Stem cells
Rats with spinal damage “cured”, but much more research is needed

Promoting Recovery by Rehabilitative Training
Constraint-induced therapy – down functioning limb while training the impaired one – create a competitive situation to foster recovery
Facilitated walking as an approach to treating spinal injury

Can the brain recover from brain damage?
Consider what you now know about the brain’s ability to adapt following brain damage, can it “recover”?
If so, what conditions promote recovery?

Pinel basics ch08

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