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Can the Brain Recover from Damage?

Topic 10 Brain Damage and Neuroplasticity1Causes of Brain DamageBrain tumorsCerebrovascular disordersClosed-head injuriesInfections of the brainNeurotoxinsGenetic factors

2Brain TumorsA 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 removable3Brain TumorsMost brain tumors are infiltratingGrow diffusely through surrounding tissueMalignant, difficult to remove or destroyAbout 10% of brain tumors are metastatic they originate elsewhere, usually the lungs4Cerebrovascular DisordersStroke a sudden-onset cerebrovascular event that causes brain damageCerebral hemorrhage bleeding in the brainCerebral ischemia disruption of blood supply3rd leading cause of death in the US and most common cause of adult disability5Cerebrovascular DisordersCerebral hemorrhage blood vessel rupturesAneurysm 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 birthCerebral ischemia disruption of blood supplyThrombosis plug formsEmbolism plug forms elsewhere and moves to the brainArteriosclerosis wall of blood vessels thicken, usually due to fat deposits6Damage due to Cerebral IschemiaDoes not develop immediately Most damage is a consequence of excess neurotransmitter release especially glutamateBlood-deprived neurons become overactive and release glutamateGlutamate overactivates its receptors, especially NMDA receptors leading to an influx of Na+ and Ca++7Damage 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 affected8

9Closed-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 blowContusions 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.10ConcussionsWhile there is no apparent brain damage with a single concussion, multiple concussions may result in a dementia referred to as punch-drunk syndromeWhen might this occur?Can it be prevented?11Brain InfectionInvasion of the brain by microorganismsEncephalitis the resulting inflammationBacterial infectionsOften leads to abscesses, pockets of pusMay inflame meninges, creating meningitisTreat with penicillin and other antibioticsViral infectionsSome viral infections preferentially attack neural tissues12Brain Infections - Some CausesBacterialSyphilis may produce a syndrome of insanity and dementia known as general paresisSyphilis bacteria are passed to the noninfected and enter a dormant stage for many years.ViralRabies high affinity for the nervous systemMumps and herpes typically attack tissues other than the brainViruses may lie dormant for years13NeurotoxinsMay enter general circulation from the GI tract, lungs, or through the skinToxic psychosis chronic insanity produced by a neurotoxin. The Mad Hatter may have had toxic psychosis due to mercury exposure14NeurotoxinsSome antipyschotic drugs produce a motor disorder caused tardive dyskinesiaRecreational drugs, such as alcohol, may cause brain damageNeurotoxic effects of alcoholThiamine deficiencySome neurotoxins are endogenous produced by the body

15Genetic FactorsMost 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

16Autistic DisorderA 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.

17Possible causesBiologicalAutism 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.18Possible causesPhenylketonuria (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 pathologyHeritable 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.19Attention-Deficit/Hyperactivity DisorderA 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.20Possible causesGeneticsThere is strong evidence from family and twin studies for hereditary factors in a persons likelihood of developing ADHD.LearningSome evidence suggests impulsive and hyperactive behaviors are a result of a steep delay of reinforcement gradient.21Possible causesBiologicalThere is evidence to suggest that abnormalities in dopaminergic transmission play a role in ADHD.Brain structuresStudies 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.22EpilepsyPrimary symptom is seizures, but not all who have seizures have epilepsyEpileptics have seizures generated by their own brain dysfunctionAffects about 1% of the populationDifficult to diagnose due to the diversity and complexity of epileptic seizures23EpilepsyTypes of seizuresConvulsions motor seizuresSome are merely subtle changes of thought, mood, or behaviorCausesBrain damageGenes over 70 known so farDiagnosisEEG ElectroencephalogramSeizures associated with high amplitude spikes24EpilepsySeizures often preceded by an aura, such as a smell, hallucination, or feelingAuras nature suggests the epileptic focusWarns epileptic of an impending seizurePartial epilepsy does not involve the whole brainGeneralized epilepsy involve the entire brain25Partial SeizuresSimplesymptoms are primarily sensory or motor or both (Jacksonian seizures)symptoms spread as epileptic discharge spreadsComplex often restricted to the temporal lobes (temporal lobe epilepsy)patient engages in compulsive and repetitive simple behaviors automatismsmore complex behaviors seem normal26Generalized SeizuresGrand malLoss of consciousness and equilibriumTonic-clonic convulsions -rigidity (tonus) and tremors (clonus)Resulting hypoxia may cause brain damagePetit malnot associated with convulsionsA disruption of consciousness associated with a cessation of ongoing behavior27Parkinsons DiseaseA movement disorder of middle and old age affecting ~ .5%of the populationPain and depression commonly seen before the full disorder developsTremor at rest is the most common symptom of the full-blown disorderDementia is not typically seenNo single cause28Parkinsons DiseaseAssociated with degeneration of the substantia nigra whose neurons use dopamineAlmost no dopamine in the substantia nigra of Parkinsons patientsTreated temporarily with L-dopaLinked to ~10 different gene mutations29Huntingtons DiseaseAlso 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 dementiaDeath usually occurs within 15 yearsCaused by a single dominant gene1st symptoms usually not seen until age 4030Multiple SclerosisA 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 commonSymptoms include visual disturbances, muscle weakness, numbness, tremor, and loss of motor coordination (ataxia)31Multiple SclerosisEpidemiological studies find that incidence of MS is increased in those who spend childhood in a cool climateMS is rare amongst Africans and AsiansStrong genetic predisposition and many genes involvedAn autoimmune disorder immune system attacks myelinDrugs may retard progression or block some symptoms32Alzheimers DiseaseMost common cause of dementia likelihood of developing it increases with ageProgressive, with early stages characterized by confusion and a selective decline in memoryDefinitive diagnosis only at autopsy must observe neurofibrillary tangles and amyloid plaques33Neuropsychological Diseases - RecapEpilepsy abnormal electrical activityParkinsons diseaseprogressive motor disorder without dementiaHuntingtons diseaseprogressive motor disorder with dementiaMultiple sclerosis autoimmune disorder that affects motor function and strikes earlyAlzheimers disease - dementia34Animal Models of Human Neuropsychological DiseasesWhile animal models only model some aspects of the human condition, they can provide insightKindling model of epilepsyExperimentally induced seizure activityTransgenic mouse model of AlzheimersMice producing human amyloidMPTP model of ParkinsonsDrug-induced damage comparable to that seen in PD35Kindling Model of EpilepsyA series of periodic brain stimulations eventually elicits convulsions the kindling phenomenonNeural changes are permanentProduced 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 timeKindling phenomenon is comparable to the development of epilepsy (epileptogenesis) seen following a head injury36MPTP Model of Parkinsons DiseaseThe Case of the Frozen AddictsSynthetic heroin produced the symptoms of ParkinsonsContained MPTPMPTP causes cell loss in the substantia nigra, like that seen in PDAnimal studies led to the finding that deprenyl can retard the progression of PD37Neuroplastic Responses to Nervous System DamageDegeneration - deteriorationRegeneration regrowth of damaged neuronsReorganizationRecovery38DegenerationCutting axons is a common way to study responses to neuronal damageAnterograde - degeneration of the distal segment between the cut and synaptic terminalcut off from cells metabolic centerswells and breaks off within a few daysRetrograde degeneration of the proximal segment between the cut and cell bodyprogresses slowlyif regenerating axon makes a new synaptic contact, the neuron may survive39Neural RegenerationDoes not proceed successfully in mammals and other higher vertebrates - capacity for accurate axonal growth is lost in maturityRegeneration is virtually nonexistent in the CNS of adult mammals and unlikely, but possible, in the PNS

40Neural Regeneration in the PNSIf the original Schwann cell myelin sheath is intact, regenerating axons may grow through them to their original targetsIf the nerve is severed and the ends are separated, they may grow into incorrect sheathsIf ends are widely separated, no meaningful regeneration will occur41Neural ReorganizationReorganization of 1 sensory and motor systems has been observed following damage to:peripheral nervesprimary cortical areasLesion one retina and remove the other V1 neurons that originally responded to lesioned area now responded to an adjacent area remapping occurred within minutesStudies show scale of reorganization possible is far greater than anyone assumed possible42How/why does damage lead to reorganization?Strengthened existing connections due to a release from inhibition?Consistent with speed and localized nature of reorganizationEstablishment of new connections?Magnitude can be too great to be explained by changes in existing connections43Recovery of Function after Brain DamageDifficult to conduct controlled experiments on populations of brain-damaged patientsCant distinguish between true recovery and compensatory changesCognitive reserve education and intelligence thought to play an important role in recovery of function may permit cognitive tasks to be accomplished new waysAdult neurogenesis may play a role in recovery44Treating Nervous System DamageReducing brain damage by blocking neurodegenerationPromoting recovery by promoting regenerationPromoting recovery by transplantationPromoting recovery by rehabilitative training45Reducing brain damage by blocking neurodegenerationVarious neurochemicals can block or limit neurodegenerationApoptosis inhibitor protein introduced in rats via a virusNerve growth factor blocks degeneration of damaged neuronsEstrogens limit or delay neuron deathNeuroprotective molecules tend to also promote regeneration46Promoting Recovery by Promoting RegenerationWhile regeneration does not normally occur in the CNS, experimentally it can be inducedEliminate inhibition of oligodendroglia and regeneration can occurProvide Schwann cells to direct growth47Promoting Recovery by NeurotransplantationFetal tissue Fetal substantia nigra cells used to treat MPTP-treated monkeys (PD model)Treatment was successfulLimited success with humansStem cellsRats with spinal damage cured, but much more research is needed

48Promoting Recovery by Rehabilitative TrainingConstraint-induced therapy down functioning limb while training the impaired one create a competitive situation to foster recoveryFacilitated walking as an approach to treating spinal injury49Can the brain recover from brain damage?Consider what you now know about the brains ability to adapt following brain damage, can it recover?If so, what conditions promote recovery?50