Chapter 10 Brain Damage and NeuroplasticityCan the Brain Recover from Damage?

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Causes of Brain Damage

Brain tumorsCerebrovascular disordersClosed-head injuriesInfections of the brainNeurotoxinsGenetic factors

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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

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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

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Figure 10-1

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Figure 10-2

Metastatic brain tumors

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Figure 10-3

Professor P’s Acoustic Neuroma

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Cerebrovascular Disorders

Stroke – a sudden-onset cerebrovascular event that causes brain damage

Cerebral hemorrhage – bleeding in the brain

Cerebral ischemia – disruption of blood supply

3rd leading cause of death in the US and most common cause of adult disability

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Cerebrovascular Disorders Cerebral hemorrhage – blood vessel ruptures

Aneurysm – a weakened point in a blood vessel that makes a stroke more likely. May be congenital or due to poison or infection.

Congenital – present at birth Cerebral ischemia – disruption of blood supply

Thrombosis – plug formsEmbolism – plug forms elsewhere and moves to the

brainArteriosclerosis – wall of blood vessels thicken, usually

due to fat deposits

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Figure 10-4

Angiogram showing narrowing of the carotid artery--the main blood pathway to the brain

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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 Na+ and Ca+

+

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Damage due to Cerebral Ischemialnflux of Na+ and Ca++ triggers:

the release of still more glutamatea sequence of internal reactions that ultimately

kill the neuronIschemia-induced brain damage

takes timedoes not occur equally in all parts of the brainmechanisms of damage vary with the brain

structure affected

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Figure 10-5

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Closed-Head InjuriesBrain 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.

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Figure 10-6

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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?

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Case 10-2

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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 infectionsSome viral infections preferentially attack neural tissues

Bacteria versus Viruses

http://cubanology.com/Articles/Virus_vs_Bacteria.htm

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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

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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

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Neurotoxins

Some antipyschotic drugs produce a motor disorder caused tardive dyskinesia

Recreational drugs, such as alcohol, may cause brain damageNeurotoxic effects of alcoholThiamine deficiency

Some neurotoxins are endogenous – produced by the body

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Genetic Factors

Most neuropsychological diseases of genetic origin are associated with recessive genes. Why?

Down syndrome0.15% of births, probability increases with

advancing maternal ageExtra chromosome 21Characteristic disfigurement, mental

retardation, other health problems

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Figure 10-7

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Neuropsychological Diseases

EpilepsyParkinson’s diseaseHuntington’s diseaseMultiple sclerosisAlzheimer’s disease

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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

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Epilepsy

Types of seizuresConvulsions – motor seizuresSome are merely subtle changes of thought, mood, or

behavior Causes

Brain damageGenes – over 70 known so far

DiagnosisEEG – ElectroencephalogramSeizures associated with high amplitude spikes

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Figure 10-8

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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

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Figure 10-9

The bursting of an epileptic neuron, recorded by extracellular unit recording.

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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

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Case 10-3

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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

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Figure 10-10

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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 seenNo single cause

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Parkinson’s DiseaseAssociated with degeneration of the

substantia nigra whose neurons use dopamine and project to the striatum of the basal ganglia

Almost no dopamine in the substantia nigra of Parkinson’s patients

Treated temporarily with L-dopa

Linked to ~10 different gene mutations

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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 severe dementia

Death usually occurs within 15 years

Caused by a single dominant gene

1st symptoms usually not seen until age 40

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Image 10-1

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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)

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Figure 10-11

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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

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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

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Figure 10-12

Amyloid Plaques in an Alzheimer Patient’s Brain

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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

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Figure 10-13

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Neuropsychological Diseases - Recap Epilepsy – abnormal electrical activity Parkinson’s disease

progressive motor disorder without dementia

Huntington’s diseaseprogressive motor disorder with dementia

Multiple sclerosis autoimmune disorder that affects motor function and

strikes early

Alzheimer’s disease - dementia

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Animal Models of Human Neuropsychological Diseases While animal models only model some aspects of

the human condition, they can provide insight

Kindling model of epilepsyExperimentally induced seizure activity

Transgenic mouse model of Alzheimer’sMice producing human amyloid

MPTP model of Parkinson’sDrug-induced damage comparable to that seen in PD

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Kindling Model of Epilepsy A series of periodic brain stimulations eventually

elicits convulsions – the kindling phenomenonNeural changes are permanent

Produced by stimulation distributed over time

Convulsions are similar to those seen in some forms of human epilepsy – but they only occur spontaneously if kindled for a very long time

Kindling phenomenon is comparable to the development of epilepsy (epileptogenesis) seen following a head injury

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Transgenic Mouse Model of AD

Transgenic – genes of another species have been introduced

Only humans and a few related primates develop amyloid plaques

Genes accelerating human amyloid synthesis introduced into micePlaque distribution comparable to that in AD

No neurofibrillary tangles

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MPTP Model of Parkinson’s DiseaseThe Case of the Frozen Addicts

Synthetic heroin produced the symptoms of Parkinson’s

Contained MPTP

MPTP causes 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

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Case 10-4

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Figure 10-14

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Neuroplastic Responses to Nervous System Damage

Degeneration - deterioration

Regeneration – regrowth of damaged neurons

Reorganization

Recovery

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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

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Figure 10-15

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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

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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

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Figure 10-16Neural Regeneration

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Figure 10-17

Collateral Sprouting

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Why do mammalian PNS neurons regenerate and CNS neurons do not?

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

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Neural Reorganization Reorganization of 1° sensory and motor systems has

been observed following damage to:peripheral nervesprimary 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

Contralateral somatosensory cortex of monkeys whose arm sensory neurons cut 10 years before--cortical face area expanded into original arm area.

Transection of motor neurons to rat vibrissae muscles Studies show scale of reorganization possible is far

greater than anyone assumed possible

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Figure 10-18Reorganization of the Rat Motor Cortex after Transection of

Motor Neurons that Control the Vibrissae (whiskers)

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Mechanisms of Neural Reorganization

Existing connections strenghtened due to a release from inhibition?

Consistent with speed and localized nature of reorganization

New connections established?

Magnitude can be too great to be explained by changes in existing connections

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Figure 10-19

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Recovery of Function after Brain Damage Poorly Understood 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

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Figure 10-20

17-20 21-25 26+ 17-21 22-25 26+ 17-19 20-25 26+

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Figure 10-21

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Treating Nervous System Damage

Reducing brain damage by blocking neurodegeneration

Promoting recovery by promoting regeneration

Promoting recovery by transplantation

Promoting recovery by rehabilitative training

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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

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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

Transplanting of olfactory sheathing cells

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Promoting Recovery by NeurotransplantationFetal tissue

Fetal substantia nigra cells used to treat MPTP-treated monkeys (PD model)

Treatment was successful

Limited success with humans

Stem cellsRats with spinal damage “cured”, but much more

research is needed

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Case 10-5

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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

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Case 10-6.1

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Case 10-6.2

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Figure 10-22

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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?