Copyright © 2007 by Allyn and Bacon Chapter 8 Brain Damage and Neuroplasticity Can the Brain Recover from Damage? This multimedia product and its contents are protected under copyright law. The following are prohibited by law: any public performance or display, including transmission of any image over a network; preparation of any derivative work, including the extraction, in whole or in part, of any images; any rental, lease, or lending of the program.

Copyright © 2007 by Allyn and Bacon Causes of Brain Damage Brain tumors Cerebrovascular disorders Closed-head injuries Infections of the brain Neurotoxins Genetic factors

Copyright © 2007 by Allyn and Bacon 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

Meningiomas Common in middle-age to elderly adults; more women than men Symptoms differ depending on the site”  Frontal Lobe  Left Side  Temporal Lobe  Parietal Lobe Copyright © 2007 by Allyn and Bacon

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 Metastasis: transmission of disease from one organ to another

Copyright © 2007 by Allyn and Bacon Cerebrovascular Disorders- Stroke – a sudden-onset cerebrovascular event that causes brain damage  Cerebral hemorrhage – bleeding in the brain  Cerebral ischemia – disruption of blood supply Damage depends on the INFARCT 3 rd leading cause of death in the US and most common cause of adult disability

Strokes Two Types of Risk Factors:  No control: Age; Gender; Race; Family History; Prior History  Can Control Diet; obesity; high blood pressure; heart disease; smoking; high cholesterol; excess alcohol intake; diabetes Copyright © 2007 by Allyn and Bacon

Transient Ischemic Attack (TIA) Short-term reduction in blood flow to the brain Symptoms: weakness or tingling in an arm or leg Usually few minutes Don’t cause brain damage but warning sign Copyright © 2007 by Allyn and Bacon

Origin and Damage of a Stroke Right Hemisphere Left Hemisphere: Aphasia Cerebellum Brain Stem Copyright © 2007 by Allyn and Bacon

Cerebrovascular Disorders Cerebral hemorrhage (20%) – 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 (80%) – disruption of blood supply  Most common  Thrombosis – plug forms  Embolism – plug forms elsewhere and moves to the brain  Arteriosclerosis – wall of blood vessels thicken, usually due to fat deposits

Copyright © 2007 by Allyn and Bacon 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

Copyright © 2007 by Allyn and Bacon 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

Copyright © 2007 by Allyn and Bacon 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.

Copyright © 2007 by Allyn and Bacon 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” Boxers at risk

Copyright © 2007 by Allyn and Bacon Brain Infection Invasion of the brain by microorganisms Encephalitis – the resulting inflammation Bacterial infections  Often leads to Cerebral Abscesses, pockets of pus  May inflame meninges, creating meningitis  Treat with penicillin and other antibiotics Viral infections  Some viral infections preferentially attack neural tissues

Copyright © 2007 by Allyn and Bacon 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. Attack the brain approximately 20 years after initial exposure. Lead to Dementia and insanity Viral Rabies – high affinity for the nervous system  Symptoms  Time between expo and Sx Mumps and herpes – typically attack tissues other than the brain Viruses may lie dormant for years

Copyright © 2007 by Allyn and Bacon 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

Copyright © 2007 by Allyn and Bacon Neurotoxins Some antipsychotic drugs produce a motor disorder caused tardive dyskinesia  Symptoms Recreational drugs, such as alcohol, may cause brain damage

Copyright © 2007 by Allyn and Bacon 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

Copyright © 2007 by Allyn and Bacon Programmed Cell Death Apoptosis – cell suicide – involved in all forms of brain damage discussed thus far Apoptosis is adaptive Ex. Rett’s Syndrome

Copyright © 2007 by Allyn and Bacon Neuropsychological Diseases Epilepsy Parkinson’s disease Huntington’s disease Multiple sclerosis Alzheimer’s disease

Copyright © 2007 by Allyn and Bacon 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

Copyright © 2007 by Allyn and Bacon 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

Copyright © 2007 by Allyn and Bacon 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  May give a clue as to the location of the tumor Partial epilepsy – does not involve the whole brain Generalized epilepsy – involve the entire brain

Copyright © 2007 by Allyn and Bacon 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  ½ of seizures fall in this category

Copyright © 2007 by Allyn and Bacon Generalized Seizures Grand mal  Loss of consciousness and equilibrium  Tonic-clonic convulsions -rigidity (tonus) and tremors (clonus)  Resulting hypoxia (shortage of oxygen) may cause brain damage Petit mal  not associated with convulsions  A disruption of consciousness associated with a cessation of ongoing behavior  Common in children and stops at puberty

Copyright © 2007 by Allyn and Bacon Parkinson’s Disease A movement disorder of middle and old age affecting ~.5%of the population 2.5 times more in males 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 No familial history

Copyright © 2007 by Allyn and Bacon 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

Copyright © 2007 by Allyn and Bacon 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; no cure Caused by a single dominant gene 1 st symptoms usually not seen until age 40

Copyright © 2007 by Allyn and Bacon 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)

Copyright © 2007 by Allyn and Bacon 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 Twice more common in females Strong genetic predisposition and many genes involved An autoimmune disorder – immune system attacks myelin Drugs may retard progression or block some symptoms

Copyright © 2007 by Allyn and Bacon 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

Copyright © 2007 by Allyn and Bacon 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

Copyright © 2007 by Allyn and Bacon 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

Copyright © 2007 by Allyn and Bacon Neuroplastic Responses to Nervous System Damage Degeneration - deterioration Regeneration – regrowth of damaged neurons Reorganization Recovery

Copyright © 2007 by Allyn and Bacon 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

Copyright © 2007 by Allyn and Bacon 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

Copyright © 2007 by Allyn and Bacon 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

Copyright © 2007 by Allyn and Bacon Neural regeneration

Copyright © 2007 by Allyn and Bacon 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

Copyright © 2007 by Allyn and Bacon 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

Copyright © 2007 by Allyn and Bacon 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

Copyright © 2007 by Allyn and Bacon Treating Nervous System Damage Reducing brain damage by blocking neurodegeneration Promoting recovery by promoting regeneration Promoting recovery by transplantation Promoting recovery by rehabilitative training

Copyright © 2007 by Allyn and Bacon 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

Copyright © 2007 by Allyn and Bacon 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

Copyright © 2007 by Allyn and Bacon 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

Copyright © 2007 by Allyn and Bacon 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

Copyright © 2007 by Allyn and Bacon 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?