1. Can the Brain Recover from Damage? Topic 10 Brain Damage and Neuroplasticity

2. Causes of Brain Damage Brain tumors Cerebrovascular disorders Closed-head injuries Infections of the brain Neurotoxins Genetic factors

3. 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

4. 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

5. 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

6. 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 forms Embolism – plug forms elsewhere and moves to the brain Arteriosclerosis – wall of blood vessels thicken, usually due to fat deposits

7. 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 ++

8. Damage due to Cerebral Ischemia lnflux of Na + and Ca ++ 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

10. 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.

11. 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?

12. 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

13. 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

14. 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

15. Neurotoxins Some antipyschotic drugs produce a motor disorder caused tardive dyskinesia Recreational drugs, such as alcohol, may cause brain damage Neurotoxic effects of alcohol Thiamine deficiency Some neurotoxins are endogenous – produced by the body

16. 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

17. Autistic Disorder A chronic disorder whose symptoms include failure to develop normal social relations with other people, impaired development of communicative ability, lack of imaginative ability, and repetitive, stereotypical movements.

18. Possible causes Biological  Autism was once believed to be acquired through interactions with hostile, withdrawn parents.  Research and mental health professionals are convinced autism is caused by biological factors.  Between 2 and 3 percent of siblings of people with autism are themselves autistic.  There is a 70 percent concordance rate for monozygotic twins.

19. Possible causes Phenylketonuria (PKU) A hereditary disorder caused by the absence of an enzyme that converts the amino acid phenylalanine to tyrosine; causes brain damage unless a special diet is implemented soon after birth. Brain pathology Heritable aspect of autism suggests the disorder is a result of structural or biochemical abnormalities in the brain. Researchers have found evidence for structural abnormalities in the brains of autistics, but so far we cannot point to any single abnormality as the cause of the disorder.

20. Attention-Deficit/Hyperactivity Disorder A disorder characterized by uninhibited responses, lack of sustained attention, and hyperactivity; first shows itself in childhood. ADHD is the most common behavior disorder that shows itself in childhood. ADHD is seen in 4 to 5% of grade school children.

21. Possible causes Genetics There is strong evidence from family and twin studies for hereditary factors in a person’s likelihood of developing ADHD. Learning Some evidence suggests impulsive and hyperactive behaviors are a result of a steep delay of reinforcement gradient.

22. Possible causes Biological There is evidence to suggest that abnormalities in dopaminergic transmission play a role in ADHD. Brain structures Studies of brain structure of people with ADHD do not reveal any localized abnormalities, though the total volume of their brains is approximately 4% smaller than normal.

23. 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

24. 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

25. 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

26. 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

27. 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

28. 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

29. 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

30. 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

31. 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)

32. 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

33. 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

34. 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

35. Animal Models of Human Neuropsychological Diseases While animal models only model some aspects of the human condition, they can provide insight Kindling model of epilepsy Experimentally induced seizure activity Transgenic mouse model of Alzheimer’s Mice producing human amyloid MPTP model of Parkinson’s Drug-induced damage comparable to that seen in PD

36. Kindling Model of Epilepsy A series of periodic brain stimulations eventually elicits convulsions – the kindling phenomenon Neural 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

37. MPTP Model of Parkinson’s Disease The 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

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

39. 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

40. 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

41. 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

42. 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

43. 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

44. 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

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

46. 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

47. 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

48. 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

49. 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

50. 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?