Pinel basics ch08

Copyright © 2007 by Allyn and Bacon

Chapter 8Brain Damage and NeuroplasticityCan 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 meningesEncapsulated, growing within their own

membranesUsually benign, surgically removable


Brain Tumors

Most brain tumors are infiltratingGrow diffusely through surrounding

tissueMalignant, 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 damageCerebral hemorrhage – bleeding in the brainCerebral ischemia – disruption of blood

supply 3rd 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 glutamatea sequence of internal reactions that

ultimately kill the neuron Ischemia-induced brain damage

takes timedoes not occur equally in all parts of the brainmechanisms 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 feelingAura’s nature suggests the epileptic focusWarns 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 malLoss of consciousness and equilibriumTonic-clonic convulsions

-rigidity (tonus) and tremors (clonus)Resulting hypoxia may cause brain damage

Petit malnot associated with convulsionsA 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 1st 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 1st – 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 regenerationNeurotrophic factors stimulate growthCAMs 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 successfulLimited success with humans

Stem cellsRats 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

Health & Medicine

brain infections

forms of brain damage

brain viruses

brain opposite

brain dysfunction

brain structure

apparent brain damage

brain mechanisms of