Chapter 9-10 PDF

lOMoARcPSD|43883818 Chapter 9: Development of the Nervous System 9.1 Phases of Neurodevelopment  Zygote: a single cell formed by the amalgamation of an ovum and a sperm o Divides to form two daughter cells...

lOMoARcPSD|43883818 Chapter 9: Development of the Nervous System 9.1 Phases of Neurodevelopment  Zygote: a single cell formed by the amalgamation of an ovum and a sperm o Divides to form two daughter cells o Then four then eight  Three things other than cells multiplication: o Cells must differentiate (muscles cells, multipolar neurons,,,, o Cells must make their way to appropriate sites and align themselves with the cells around them to form particular structures o Cells must establish appropriate functional relations with other cells  Induction of the neural plate  Neural proliferations  Migration and aggregation  Aon growth and synapse formation  Neuron death and synapse rearrangement Induction of the neural plate  Neural plate – a small patch of ectodermal tissue on the dorsal surfaceof the developing embryo o Is the first major stage of neurodevelopment in all vertebrates  Ectoderm  mesoderm  endoderm  The development seems to be induced by chemical signals from an area of the underlying mesoderm layer (area that is consequently referred to as an organizer)  Experiment: tissue taken form the dorsal mesoderm of one embryo and implanted beneath the ventral ectoderm of another embryo induces the development of an extra neural plate on the ventral surface of the host  An import change occurs to the cells of the developing nervous system at about the time that the neural plate becomes visible  The earliest cell: totipotent, have the ability to develop into any type of cell in the body if transplanted to the appropriate site  When neural plate develops,  cells lose some of their potential to become different kinds of cells o Each of the early neural plate still has the potential to develop into mist types of mature nervous system cell, but cannot normally develop into other kinds of cells o These are said to be multipotent, rather than totipotent  Cells of the neural plate are often referred to as embryonic stem cells  Stem cells are cells that meet two specific criteria Downloaded by Marianne Audrey Pinili ([email protected])  lOMoARcPSD|43883818 o Have a seemingly unlimited capacity for self renewal if maintained in an appropriate cell culture, o They have the ability to develop into different types of mature cells  As the neural plate develops into the neural tube, some of its ells become specified as future glial cells of various types, and others become specified as future neurons of various types o Because these still have the capacity for unlimited self renewal and are still multipotent, these cells are termed glial stem cells and neural stem cells, respectively  The neural plate folds to form the neural groove, and then the lops of the neural groove fuse to form the neural tube  The inside of the neural tube eventually becomes the cerebral ventricles and spinal canal  By 40 days after conception, three swellings are visible at the anterior end of the human neural tube o These develop into the forebrain, midbrain and hindbrain Neural Proliferation  Does not occurs simultaneously or equally in all parts of the tube  Most cell division in the neural tube occurs in the ventricular zone – the region adjacent to the ventricle  The cells in different parts of the neural tube proliferate in a particular sequence that is responsible for the pattern of swelling and folding that fives the brain of each member of that species the characteristic shape  The complex pattern of proliferation is in part controlled by chemical signals from two organizer areas in the neural tube: the floor plate, which runs along the midline of the anterior surface of the tube. o The roof plate which runs along the midline of the dorsal surface of the tube Migration and Aggregation  Migration: during this period the cells are still in an immature form. Lacking the processes that characterize mature neurons o Two major factors govern migration in the developing neural tube: time and location o Cell migration in the developing neural tube is considered to be of two kinds  Radial migration proceeds from the ventricular zone in a straight line outward to ward the outer wall of the tube  Tangential migration occurs at a right angle to radial migration. That is parallel to the tube’s walls o Most cells engatge in both to get to their target destination o There are two methods by which developing cells migrate  Somal translocation, an extension grows from te developing cell in the general direction of the migration; the extension seems to explore the immediate environment for attractive and repulsive cues as it grows Downloaded by Marianne Audrey Pinili ([email protected])  lOMoARcPSD|43883818  Then the cell body itself moves into and along the extending process, and trailing processes are retracted  Glia mediate migration – once the period of neural proliferation is well underway and the walls of the neural tube are thickening, a temporary network of glial cells, called radial glial cells, appears in the developing neural tube  Most engaging in radial migration do so by moving a long the radial glial network  Inside out pattern: the pattern of cortical development in which orderly waves of tangential migrations progress systematically from deeper to more superficial layers o The patterns of proliferation and migration are different for different areas of the cortex o Neural crest: structure that is situated just dorsal to the neural tube  Fromed from cells that break off from the nueral tube as It is being formed  Develop into the neurons and glial cells of the peripheral nervous system, and thus many of them must migrate over considerable distances  Aggregation: once migrated, neurons must align themselves with other developing neurons that have migrated to the same area to form the structure of the nervous system o Both migration and aggregation re thought to be mediated by cell adhesion molecules (CAMs) – located on the surfaces of neurons and other cells  Cell adhesion molecules have the ability to recognize molecules on other cells adhere to them o Gap junctions found to be particularly prevalent during brain development  Not was wide as synapses, and the gaps are bridged by narrow tubes called connexins, through which cells can exchange cytoplasm Axon Growth and Synapses Formation Axon Growth  At each growing tip of an axon or dendrite is an amoebalike structure called a growth cone, which extends and retracts fingerlike cytoplasmic extensions called filopodia  Study: cut the optic nerves of frogs, rotated their eyeballs 180 degree, and waited for the axons of the retinal ganglion cells, which compose the optic nerve, to regenerate o Once regeneration was complete  test the visual capacities o When dangled a lure behind the frogs. They struck forward, thus indicating that their visual world had been rotated like their eyes o Frogs whose eyes had been rotated, but whose optic nerves had into been cut, responded in exactly the same way Downloaded by Marianne Audrey Pinili ([email protected])  lOMoARcPSD|43883818  This study was strong behavior evidence that each retinal ganglion cell had grown back to the same point f the optic tectum (called the superior colliculus in mammals) to which it had originally been connected  Chemoaffinity hypothesis of axonal development: each postsynaptic surface in the nervous system releases a specific chemical label and that each growing axons is attracted y the level to its postsynaptic target during both neural development and regeneration o This fails to account for the discovery that some growing axons follow the same circuitous route to reach their target in every member of a species, rather than growing directly to it o Leads to revise version  Revised version: a growing axon is not attracted to its target by a single specific attractant released by the target o Instead, growth cones seem to be influenced by a series of chemical signals along the route o These guidance molecules are similar to those that guide neural migration in the sense that some attract and other repel the growing axons  Pioneer growth cones – the first growth cones to travel along a particular route in a developing nervous system – are presumed to follow the correct trial by interacting with guidance molecules along the route. o Subsequent growth cones embarking on the same journey follow the routes blazed by the pioneers o The tendency of developing axons to grow along the paths established by preceding axons is called fasciculation  The topographic Gradient hypothesis has been proposed tot explain accurate axonal growth involving topographic mapping in the developing brain o Axons growing from one topographic surface to another are duided to specific targer that are arranged on the terminal surface in the same way sas the axons’ cell bodies are arranged on the original surface o The key part is that they growing axons are guided to their destinations by two intersecting signal fradeitns o Several guidance molecules have been implicated in signal gradients  The evidence is strongest for a family of molecules called ephrins Synapse Formation  The most exciting recent discovery about synaptogenesis (the formation of synapses) : o Depends on the presence of glial cells, particularly astrocytes o Retinal ganglion cells maintained in culture formed seven times more synapses when astrocytes were present Downloaded by Marianne Audrey Pinili ([email protected])  lOMoARcPSD|43883818 o Synapses formed in the presence of astrocytes were quickly lost when the astrocytes were removed o Early theories about the contribution of astrocytes to synaptogenesis emphasize a nutritional role: developing neurons need high levels of cholesterol during synapse formation  Developing neurons need high levels of cholesterol during synapse formation, and thee extra cholesterol is supplied by astrocytes o Current evidence: astrocytes play a much more extensive role in synaptogenesis by processing, transferring, and storing information supplied by neurons o Most current: focusing on elucidating the chemical signals that must be exchanged between presynaptic and postsynaptic neurons for a synapse to be created Neuron Death and Synapse Rearrangement Neuron Death: about 50% are produced than are required, and large-scale neuron death occurs in waves in various parts of the brain throughout development  Cell death is active o Genetic programs inside neurons are triggered and cause them to actively commit suicide  Passive cell death is called necrosis o Cells break apart and spill their contents into extracellular fluid, and the consequence is potentially harmful inflammation  Active called apoptosis o Safer – DNA and other internal structures are cleaved apart and packaged in membranes before the cell breaks apart o These membranes contain molecules that attract scavenger microglia and other molecules that prevent inflammation o Removes excess neurons in a safe, neat and orderly way  If generic programs are blocked  cancer, o Inappropriately activated  can be neurodegenerative disease  Two kinds of triggers apoptosis o Some developing neurons appear o be genetically programmed for an early death – once they have fulfilled their functions, groups of neurons die together, in the absence of any obvious external stimulus o Some developing neurons seem to die because they fail to obtain the life preserving chemicals that are supplied by their targets Downloaded by Marianne Audrey Pinili ([email protected])  lOMoARcPSD|43883818  Evidence that life preserving chemicals are supplied to developing neurons by their postsynaptic targets comes from two kinds of observations: o Grafting an extra target structure to an embryo before the period of synaptogenesis reduces the death of neurons growing into the area, and destroying some of the neurons growing into an are before the period of cell death increases the survival rate of the remaining neurons  Neurotrophins: prominent class of life preserving chemicals that are supplied to developing neurons o Nerve growth Factor (NGF) was the first neurotrophin to be isolated o Promote the growth and survival of neurons, function as axon guidance molecules, and stimulate synaptogenesis Synapse Rearrangement  As neurons die, the space they leave vacant on postsynaptic membrane is filled by the sprouting axon terminals of surviving neurons o Thus results in a massive rearrangement of synaptic connections  This phase tends to focus the output of each neuron on a smaller number of postsynaptic cells, thus increasing the selectivity of transmission 9.2 Postnatal Cerebral Development in Human Infants Postnatal Growth of the Human brain  Volume quadruples between birth and adulthood  This increase in size does not result from the development of additional neurons  With the exception of two structures – olfactory bulb and the hippocampus o In which many new neurons continue to be created during the adult years, all of the enurons that will compose the adult human brain have developed by the seventh month of prenatal development  The postnatal growth seem s to result from three other kinds of growth: synaptogenesis, myelination of axons, and increased branching of dendrites  There is a general increase in synaptogenesis in the human cortex shortly after birth, but there are differences among the cortical regions o In the primary visual and auditory cortexes, there is a major burst of synaptogenesis in the fourth postnatal month, and maximum synapse density is achieved in the seventh or eight postnatal month; whereas synaptogenesis n the prefrontal cortex occurs at a relatively steady rate, reaching maximum synapse density in the second year  Myelination increases the speed of axonal conduction, and the myelination of various areas of the human brain during development roughly parallels their functional development Downloaded by Marianne Audrey Pinili ([email protected])  lOMoARcPSD|43883818 o Of the sensory areas occurs in the first few months after birth, and myelination of the motor areas follows soon after o Myelination of prefrontal cortex continues into adulthood  The pattern of dendritic branching duplicates the original pattern of neural migration – dendritic branching progresses from deeper to more superficial layers  Dendrites can reconfigure themselves the speed with which even mature dendrites can change their shape (quick changes)  Once maximum synaptic density has been achieved, there are periods of synaptic loss o Occurs at different times in different parts of the brain o Synaptic density in primary visual cortex declines to adult levels by about 3 years of age o Overproduction of synapses may underlie the greater plasticity of the young brain  Cortical white matter grows slowly and steadily until early adulthood  The growth patter of cortical gray matter is an inverted U o Grows until it is larger than it will be in the adult brain then decreases in sixe  The achievement of the adult level of gray matter in a particular cortical are is correlated with that area’s reaching functional maturity – sensory and motor areas reach their mature form before cognitive areas Development of the Prefrontal cortex  Various parts of the adult prefrontal cortex seem to play roles in o Working memory – keeping relevant information accessible for short periods of time while a task is being completed o Planning and carrying out sequences of actions o Inhibiting responses that are inappropriate in the current context but not in others o Following rules for social behaviour  Youngs do not begin to demonstrate these cognitive functions until prefrontal development has progressed  Piaget studies o Keep reaching the screen that have been used to hide toys consecutively when the toy is actually hidden behind the other screen – preservation error (between 7 to 12 moths) o Preservation is the tendency to continue making a formerly correct response when it is currently incorrect  Diamond hypothesized that this preservative error occurred in infants between 7 and 12 months bc the neural circuitry of the prefrontal cortex is not yet fully developed during that period Downloaded by Marianne Audrey Pinili ([email protected])  lOMoARcPSD|43883818  Correct performance of the task involved two of the major functions of this brain area holding information in working memory and suppressing previously correct, but currently incorrect, responses.  Diamond tested monkey 7 to 12 months – make the same mistakes o Tested adult monkeys with bilateral lesions to their dorsolateral prefrontal cortex and found that the lesioned adult monkeys made perseverative errors s similar to those made by the infant monkeys 9.3 Effects of Experience on the Early Development, Maintenance and Reorganization of Neural Circuits  Permissive experiences are those that are necessary for information in genetic programs to be manifested  Instructive experiences are those that contribute to the direction of development  An important feature of the effects of experience on development is that they are time dependent o Depends on when it occurs during development o Critical period: absolutely essential for an experience to occur within a particular interval to influence development o Sensitive period: an experience has a great effect on development when it occurs during a particular interval but can still have weak effects outside the interval o The majority of experiential effects on development have sensitive periods Early Studies of Experience and Neurodevelopment: Deprivation and Enrichment  Most focus on sensory and motor  Early research focused on two general manipulations of experience sensory deprivation nd enrichment  Sensory deprivation- Rats reared from birth in the dark were found to have fewer synapses and fewer dendritic spines in their primary visual cortexes, and as adults they were found to have deficits in depth and pattern vision  Enrichment had beneficial effects – rats that were raised in enriched group cages found to have thicker cortexes with more dendritic spines and more synapses per neuron Competitive Nature of Experience and Neurodevelopment: Ocular Dominance Columns  Depriving one eye of input for a few days early in life has a lasting adverse effect on vision in the deprived eye, but doesn’t happen if the other eye is also blindfolded  When only one eye is blindfolded – the ability of that eye to activate the visual cortex is reduce, the ability of the other is increased  Both of these effects occur because early monocular deprivation changes the pattern of synaptic input into layer IV of the primary visual cortex  In many species, ocular dominance columns in layer IV of the primary visual cortex are almost fully developed at birth Downloaded by Marianne Audrey Pinili ([email protected])  lOMoARcPSD|43883818  If just one eye is deprived of light for several days at some point during the first few months of life, the system is reorganized o The width of the columns f input from the deprived eye is decreased o The width of the columns of input form the nondeprived eye is increased o The timing for this is specific to each species – it is a sensitive period because monocular deprivation in adult hood can have modest effects on ocular dominance columns  A few days of monocular deprivation produce a massive decrease in the axonal branching of the lateral geniculate nucleus neurons that normally carry signals from the deprived eye to layer IV of the primary visual cortex Effects of Experience on Topographic Sensory Cortex Maps  Three demonstration o Surgically altered the course of developing axons of ferret’s retinal ganglion cells so that the axons synapsed in the medial geniculate nucleus of the auditory system instead of in the lateral geniculate nucleus of the visual system  The experience of visual input caused the auditory cortex to become organized retinotopically  Surgically attaching the inputs of one sensory system to cortex that would normally develop into the primary cortex of another system leads that cortex to develop many, but not all, characteristics typical of the newly attached system o Raised barn owls with vision displacing prisms over their eyes  Led to corresponding change in the auditory spatial map in the tectume  Shifted its visual world 230 to the right, had an auditory map that was also shifted 23 to the right  so that objects were heard to be where they were seen to be o Several studies have shown that early music training influences the organization of human cortex  Early musical training expands the area of auditory cortex that responds to complex musical tones Experience Fine Tunes Neurodevelopment  Long before the nervous system is fully developed, neurons begin to fire spontaneously and begin to interact with the environment  The resulting of neural activity fine tune subsequent stages of neurodevelopment  This fine tuning constitutes the critical, final phase of normal development 9.4 Neuroplasticity in Adults Neurogenesis in Adults Mammals Downloaded by Marianne Audrey Pinili ([email protected])  lOMoARcPSD|43883818  Researchers have found that brain structures involved in singing begin to grow in songbirds just before each mating season and that this growth results from an increase in the number of neurons o This stimulated the reexamination of earlier unconfirmed claims that new neurons are created in the adult rat hippocampus  Research shows that adult neurogenesis does occur in the rat hippocampus – new neurons are also continually added to adult rat olfactory bulbs  In adult mammals, substantial neurogenesis seems to be restricted to the olfactory bulbs and hippocampuses – claims of adult neurogenesis in other part of the mammalian brain remain controversial  New olfactory bulb neurons and new hippocampal neurons come from different places o New olfactory bulb neurons are created from adult neural stem cells at certain sites in the sub ventricular zone of the lateral ventricles and then migrate to the olfactory bulbs o New hippocampal cells are created near their final location in the dentate gyrus of the hippocampus  Adult rats living in enriched environments produced 60% more new hippocampal neurons than did adult rats living in nonenriched environments o Observed positive effect on neurogenesis I hippocampus depends largely on the increases in exercise that typically occur in enriched environments  Since the hippocampus is involved in some kinds of memory, perhaps exercise can be used as a treatment for memory problems  Aerobic exercise has been shown to improve cognitive function in older adults  It is now established that neurons generated during adulthood survive, become integrated into neural circuits, and begin to conduct neural signals o Adult generated olfactory neurons become interneurons, o Adult generated hippocampal neurons become granule cells in the dentate gyrus Effects of Experience on the Reorganization of the Adult Cortex  Experience in adult hood can lead to reorganization of sensory and motor cortical maps o Found that tinnitus produces a major reorganization of primary auditory cortex o Showed that adult musicians who play stringed instruments that are fingered with left hand have an enlarge hand representation area in their right somatosensory cortex o Anesthetizing the second and fourth fingers reduced their representation in contralateral somatosensory cortex 9.5 Disorders of Neurodevelopment Downloaded by Marianne Audrey Pinili ([email protected])  lOMoARcPSD|43883818 Autism  Is a complex neurodevelopmental disorder  It is a difficult disorder to define because cases differ so greatly  Core symptoms: o A reduced ability to interpret the emotions and intentions of others o A reduced capacity for social interaction and communication o A preoccupation with a single subject or activity  Characteristics that tedn to occur o 80% are male, 50% suffer mental Retardation and 35% have seizures o Older mothers – more likely to five birth to a child with autism o The probability of a young mother giving birth to a child with autism increases if the father is over 40  Asperger’s syndrome – a mild autism spectrum disorder in which cognitive and linguistic functions are well preserved  Autism spectrum disorders with two main early signs: o Delayed development of language o Delayed development of social interaction  Many display minor anomalies of ear structure: square shaped ears positioned too low on the head and rotated slightly backward with the tops flopped over  Autism spectrum – the most prevalent childhood neurological disorders Autism is a Heterogeneous Disorder – is heterogeneous in the sense that afflicted individuals may be severely impaired in some respects but may be normal, or even superior, in others  Patients who suffer from mental retardation often perform well on tests involving rote memory, jogsaw puzzles, music and art  Heterogeneous pattern of deficits in speech disability o Have sizable vocabularies, are good spellers and can read aloud textual material they do not understand o However, the same indis are often unable to use intonation to communicate emotion, to coordinate facial expressions with speech, and to speak metaphorically Autistic Savants – the single most remarkable aspect – the tendency for some to be savants  Savants are intellectually handicapped indis display amazing and specific cognitive or artistic abilities  About 10% of indis with autism display some savant abilities  About 50% of savants are diagnosed with autism  Savant abilities can take many forms Downloaded by Marianne Audrey Pinili ([email protected])  lOMoARcPSD|43883818 o Feats of memory o Naming the day of eh week for any future or past date o Identifying prime numbers o Drawing and playing musical instruments Genetic Basis of Autism  Siblings of ppl with autism have about a 5% chance of being diagnosed with the disorder  If one monozygotic twin is diagnosed with autism, the other has a 60% chance of receiving the same diagnosis o Suggests that autism is triggered by several genes interacting with the environment, and several genes have already been implicated Neural Mechanisms of Autism  Two lines of research on the neural mechanism of autism spectrum disorders warrant mention – both inspired by the severe deficits in social interaction displayed by most children with such disorders o The first has focused on the abnormal; reaction of individuals with autism to faces – spend less time than normal looking at faces, particularly at the eyes  Has shownt aht the fusiform face area of autistic patietns displays less fMRi activity in response to the presentation fo faces o The second line of research focuses on mirror neurons  There is indirect evidence of mirror neurons in humans and they are believed to be part of system that helps one understand the intentions of others  Was hypothesized that children with autism might be deficient in mirror neuron function  Areas of the cortex that normally display fMRI activity when healthy volunteers observe others perfomrning tasks do not become active in children with autism, even in those with no mental retardation William Syndrome  Like autism, is a neurodevelopmental disorder associated with mental retardation and a heterogeneous pattern of abilities and disabilities  Patients are sociable, empathetic and talkative  Opposite  1 of 7500  Although they display a delay in language development and language deficits in adulthood, their language skills are remarkable considering their characteristically low IQs – which average around 60 Downloaded by Marianne Audrey Pinili ([email protected])  lOMoARcPSD|43883818  The verbal and social skills of these children often leads teachers to overestimate their cognitive abilities, and thus they do not always receive the extra academic support they need  Other cognitive strength, several of which involve music  Severe cognitive abilities – their spatial abilities are even worse than those of ppl with comparable IQs o Great difficulty remembering the location of a few blocks placed on a test board, their space related speech is poor, and their ability to draw objects is almost nonexistent  Health problems involving the heart  One heart disorder was found to result from a mutation in gene on chromosome 7 that controls the synthesis of elastin, a protein that imparts elasticity to many organs and tissues, including the hear o The same cardiac problem is prevalent in ppl with Williams syndrome o Found that the gene on one of the two copies of chromosome 7 was absent in 95% of the indis with Williams syndromes  Show general thinning of the cortex and underlying white matter  The cortical thinning is greatest in two areas at the boundary of parietal and occipital cortex and in the orbitofrontal cortex  Lack of cortical development in these two areas may be related to two of the major symptoms of Williams syndrome o Profound impairment of spatial cognition and remarkable hypersociability, respectively  Conversely, the thickness of the cortex in one area in ppl with Williams syndrome if often normal o The superior temporal gyrus, which includes primary and secondary auditory cortex  The normalcy of this area may be related to the relatively high levels of language and music processing in those with Williams syndrome  Features: short with small upturned noses, oval ears, broad mouths, full lops, puffy eyes, and small chins Downloaded by Marianne Audrey Pinili ([email protected])  lOMoARcPSD|43883818 Chapter 10 Brain Damage and Neuroplasticity Can the Brain Recover from Damage? 10.1 Causes of Brain Damage Brain Tumors  A tumor, or neoplasm, is a mass of cells that grows independently of the rest of the body  Meningiomas – tumors that grow between the meninges, the three membranes that cover the central nervous system (about 20%) o All are encapsulated tumors – tumors that grow within their own membrane o Easy to indentify on a CT scan o Influence the function of the brain by the pressure they exert on surrounding tissue o Almost always benign tumors – surgically removable with little risk of further growth in the body  Most brain tumors are infiltrating tumors – those that grow diffusely through surrounding tissue o Usually malignant tumors 0 difficult to remove or destroy them completely, and nay cancerous tissue that remains after surgery continues to grow  About 105 do not originate in the brain o Grow from infiltrating cells that are carried to the brain by the bloodstream from some other part of the body – called metastatic tumors o Metastasis – transmission of disease form one organ to another  Acoustic neuromas – encapsulated tumors that grow on cranial nerve VIII Cerebrovascular Disorders: Strokes  Strokes: sudden onset cerebrovascular disorders that cause brain damage  Third leading cause of death. The major cause of neurological dysfunction and the most common cause of adult disability  Common consequences: amnesia, aphasia. Paralysis, and coma (depend on the area of the brain)  Infarct: area of dead or dying tissue produced by a stroke o Surrounding this is a dysfunctional area called the penumbra  Tissue in penumbra may recover or die. Depending on a variety of factors, and the goal of treatment following stroke is to save it Two major types: Cerebral Hemorrhage – occurs when a cerebral blood vessel ruptures and blood seeps into the surrounding neural tissue and damages it  Bursting aneurysms are a common cause if intracerebral hemorrhage Downloaded by Marianne Audrey Pinili ([email protected])  lOMoARcPSD|43883818  An aneurysm: pathological balloonlike dilation that forms in the wall of an artery at a point where the elasticity of the artery wall is defective o Can occur in any part of the body o Can be congenital (present at birth) o Can result from exposure to vascular poisons or infection o Patients should avoid high blood pressure or any strenuous activity (weight lifting) Cerebral Ischemia: is a disruption of the blood supply to an area of the brain  The three main causes of cerebral ischemia are thrombosis, embolism, and arteriosclerosis  Thrombosis: a plug called a thrombus is formed and blocks blood flow at the site of its formation o Thrombus may be composed of a blood clot, fat, oil, and air bubble, tumor cells, or any combination thereof  Embolism is similar, except that the plug, called an embolus in this case, is carried by the blood from a larger vessel, where it was formed, to a smaller one, where it becomes lodged.  Arteriosclerosis, the walls of blood vessels thicken and the channels narrow. Usually as the result of fat deposits o This narrowing can eventually lead to complete blockage o the blood vessels  Much of the brain damage associated with stroke is a consequence of excessive release od excitatory amino acid neurotransmitters, glutamate, the brain’s most prevalent excitatory neurotransmitter o Blocked blood vessels  blood derived neurons become overactive and release excessive quantities of glutamate  gl8tatmate overactivates glutamate receptors (NMDA)  large number of NA+ and CA2+ ions enter the postsynaptic neurons o The excessive internal concentrations of sodium and calcium affect the postsynaptic neurons in two ways  Trigger the release of excessive amounts of glutamate from the neurons. Thus spreading the toxic cascade to yet other neurons.  Trigger a sequence of internal reactions that ultimately kill the postsynaptic neurons  Ischemia induced brain damage has three important properties o Takes a while to develop. Soon after a temporary cerebral ischemic episode, there usually is little or no evidence of brain damage – substantial neuron loss can often be detected a day or two later o Does not occur equally in all parts of the brain  Susceptible are neurons in certain areas of the Hippocampus o The mechanisms of damage vary somewhat from structure to structure within the brain. And in at least some areas, astrocytes have been implicated Downloaded by Marianne Audrey Pinili ([email protected])  lOMoARcPSD|43883818 Close head Injuries  Brain injuries produced by blows that do not penetrate the skull are called closed-head injuries  Contusions are closed head injuries that involve damage to the cerebral circulatory system o Produces internal hemorrhaging, which results in a hematoma – is a localized collection of clotted blood in an organ or tissue  Contusions from closed head injuries occur when the brain slams against the inside of the skull o Blood from such injuries can accumulate in the subdural space – the space between dura mater and arachnoid membrane – and severely distort the surrounding neural tissue  Contusions frequently occur on the side of the brain opposite the side struck by a blow o The reason for Contrecoup Injuries is that the blow causes the brain to strike the inside of the skull on the other side of the head  When there is a disturbance of consciousness following a blow to he head and there is no evidence of a contusion or other structural damage, the diagnosis is concussion  The Punch Drunk Syndrome is the dementia and cerebral scarring observed in boxers and other individuals who experience repeated concussions Infections of the Brain  Encephalitis: inflammation  There are two common types: bacterial infections and viral Bacterial Infections  Often lead to the formation of cerebral abscesses – pocket of pus in the brain  Bacteria are also the major cause of meningitis (fatal in 25% of adults)  Penicillin and other antibiotics sometimes eliminate bacterial infections o the rbain. But they cannot reverse brain damage that has already been produced  Syphilis bacteria are passed from infected to noninfected individuals through contact with genital sores o Then go into a dormant stage for several years before they become virulent and attack many parts of of the body, including the brain o The syndrome of insanity and dementia that results from a syphilitic infection is called general paresis Viral Infections: there are two types of viral infections – those that have a particular affinity for neural tissue and those that attack neural tissue but have no greater affinity for it than for other tissues  Rabies, usually transmitted through the bite of a rabid animal, has a articular affinity for the nervous system Downloaded by Marianne Audrey Pinili ([email protected])  lOMoARcPSD|43883818 o Although the effects of the rabies virus on the brain are almost always lethal, the virus does have one redeeming feature: it does not usually attack the brain for at least a month after it has been contracted, thus allowing time for a preventive vaccination  Mumps and herpes – attack nervous system but have no special affinity for it o Sometimes spread into the brain. Typically attack other tissues of the body  Their involvement in the etiology of disorders is often difficult to recognize because they can lie dormancy for many years before producing symptoms Neurotoxins  Toxic psychosis – chromic insanity produced by a neurotoxin  Sometimes, drugs used to treat neurological disorders prove to have toxic effects o Tardive Dyskinesia (TD) – primary symptoms are involuntary smacking and sucking movements of the lips. Thrusting and rolling of the tongue, lateral jaw movements, and puffing of the cheeks  Some are endogenous – blood can produce antibodies that attack particular components of the nervous system Genetic Factors  Normal 23 chromosomes  Most neuropsychological disease of genetic origin are cased by abnormal recessive genes that are passed form parent to offspring  Inherited neuropsychological disorders are rarely associated with dominant genes because dominant genes that disturb neuropsychological function tend to be eliminated form the gene poo; - every individual who carries one has major survival and reproductive disadvantages  Inherit one abnormal – do not develop the disorder and gene is passed on  Down syndrome – an extra chromosome 21 is created in the egg o Three of this rather than two in zygote o Probability of giving birth to a child with down syndrome increase markedly with advancing maternal age Programed Cell Death  Cell deal is not an either or situation: some dying cells display signs of both necrosis and apoptosis  Apoptosis is clearly more adaptive than necrosis  In necrosis, the damaged neuron swells and breaks apart beginning in the axons and dendrites and ending in the cell body o This fragmentation leads to inflammation  which can damage other cells in the vicinity o Necrosis is quick (complete in a few hours) Downloaded by Marianne Audrey Pinili ([email protected])  lOMoARcPSD|43883818  Apoptotic cell death is slow (day or two) o Proceeds gradually, starting with shrinkage of the cell body o As parts of the neuron die, the resulting debris is packaged in vesicles o No inflammation and damage to nearby cells is kept to a minimum 10.2 Neuropsychological diseases Epilepsy  The primary symptom is epileptic seizure  Such on time convulsion could be triggered by exposure to a convulsive toxin or by a high fever  Thus the diagnose of epilepsy is applied to only those whose seizures are repeatedly generated by their own chronic brain dysfunction  Many seizures do not take the form of convulsions –often involve tremors (clonus), rigidity (tonus), and loss of both balance and consciousness  Many involve subtle changes of thought mood, or behaviour that are not easily distinguishable from normal ongoing activity  Many cases associated with faults at inhibitory synapses that cause many neurons in a particular are to fire in synchronous bursts, a pattern of firing that is rare in the normal brain  Diagnosis rests heavily on evidence from EEG o Associated with high EEG spikes  Some epileptics experience peculiar psychological changes just before a convulsion, called epileptic auras o May take many different forms – bad smell, a specific thought, a vague feeling of familiarity, a hallucination, or a tightness of the chest  Epileptic auras are important for two reasons o The nature of the auras provides clues concerning the location of the epileptic focus o Epileptic auras can warn the patient of an impending convulsion Partial Seizures – is a seizure that does not involve the entire brain  Epileptic neurons at a focus begin to discharge together in bursts, and it is this synchronous bursting of neurons that produces epileptic spiking in the EEG  The synchronous activity tends to spread to other areas of the brain – in the case of partial seiures. Not to the entire brain  The specific Behavioural symptoms of a partial epileptic seizure depend on where the disruptive discharges begin and into what structures they spread  There are two major forms Downloaded by Marianne Audrey Pinili ([email protected])  lOMoARcPSD|43883818 o Simple partial seizures: symptoms are primarily sensory or motor or both – sometimes called Jacksonian seizures  As the epileptic discharges spread through the sensory or motor areas of the brain. The symptoms spread systematically through the body o Complex partial seizures often restricted to the temporal lobes, and those who experience them are often said to have temporal lobe epilepsy  Patient engages in compulsive, repetitive, simple behaviours commonly referred to as automatisms and in more complex behaviours that appear almost normal Generalized Seizures – involve the entire brain  Occur in many forms  One is the grand mal seizure – primary symptoms are loss of consciousness, loss of equilibrium, and a violent tonic-clonic convulsion – a convulsion involving both tonus and clonus o Tongue biting, urinary incontinence, and cyanosis (turning blue from excessive extraction of oxygen from the blood during the convulsion) o Hypoxia can also cause brain damage  Petit mal seizure – associated with convulsions; their primary behavioral symptom is the petit mal absence – a disruption of consciousness that is associated with a cessation of ongoing behaviour, a vacant look and sometimes fluttering eyelids o The EEG is different – it is a bilaterally symmetrical 3 –per-second spike and wave discharge o Most common in children, and they frequently cease at puberty o Often go undiagnosed; thus children with petit ma; epilepsy are sometimes considered to be day- dreamers Parkinson’s disease  Is a movement disorder of middle and old age that affects 1-2% of the elderly population  More prevalent in males  The initial symptoms of parkinson’s disease are mild, but inevitably increase in severity with advancing years  The most common symptoms – tremor, pronounced during inactivity but not during voluntary movement or sleep, muscular rigidity, difficulty initiating movement, slowness of movement, and a masklike face  Pain and depression often develop before the motor symptoms become severe  Dementia is not typically associated Downloaded by Marianne Audrey Pinili ([email protected])  lOMoARcPSD|43883818  Seems to have no single cause, faulty genes, and brain infections strokes, tumors, traumatic brain injury and neurotoxins have all been implicated in specific cases  Associated with widespread degeneration, but it is particularly severe in the substantia nigra – the midbrain nucleus whose neurons project via the nigrostriatal pathway to the striatum of the basal gagglia  Dopamine is normally the major neurotransmitter released by most neurons of the substantia nigra, there is little dopamine in the substantia nigra and striatum of long term parkinson’s patients  Autopsy often reveals clumps of proteins in the surviving dopaminergic neurons of the substantia nigra o The clumps are called Lewy Bodies  The symptoms of parkinson’s disease can be alleviated by injections of L-dopa – the chemical from which the body synthesizes dopamine o L-dopa is not a permanent solution; it typically becomes less and less effective with continued use. Until its side effects outweigh its benefits  About 10 different gene mutations have been linked to parkinson’s disease o These genes has been discovered in different families, each of which had members suffering from a rare familial form of early onset parkinson’s disease o Thus these mutations are unlikely to be significant factors in typical forms of the disease o The study of the effects of these gene mutations is leading to a better understanding of the physiological changes that underlie the symptoms of the disorder o All of the mutations have been found to disrupt the function of mitochondria  One of the most controversial treatments for this is deep brain stimulation, a treatment in which low intensity electrical stimulation is continually applied to an are of the brain through a stereotaxically implanted electrode o Usually involves chronic bilateral electrical stimulation off a nucleus that lies just beneath the thalamus and is connected to the basal ganlia: the subthalamic nucleus o High frequency electrical stimulation is employed, which blocks the function of the target structure, much as a leision would o Current on – symptoms are alleviated within minutes o Effectiveness of this slowly declines, improvement relative to the patient’s pretreatment status is often still apparent 2 years after o Can cause side effects such as cognitive, speech, and gait problems Huntington’s Disease  Is a progressive motor disorder of middle and old age, but it is rare  Has a strong genetic basis and is associated with severe dementia  The first sign is often increased fidgetiness Downloaded by Marianne Audrey Pinili ([email protected])  lOMoARcPSD|43883818  As the disorder develops, Rapid, complex, jerky movements of entire limbs begin to predominate  Eventually, motor and intellectual deterioration become so severe that sufferers are incapable of feeding themselves, controlling their bowels, recognizing their own children  There is no cure – death typically occurs about 15 years after the appearance of the first symptoms  Passed on by a single dominant gene, called huntingtin, protein is huntingtin protein  Often passed from parent to child because the first symptoms of the disease do not appear until after the peak reproductive years o At about age 40 Multiple Sclerosis  Is a progressive disease that attacks the myelin of axons in the CNS  Typically attacks young people just as they are beginning their adult life  First, there are microscopic areas of degeneration on myelin sheaths; but eventually damage to the myelin is so severe that the associated axons come dysfunctional and degenerate  Ultimately, many areas of hard scar tissue develop in the CNS  Is an autoimmune disorder – body’s immune system attacks part of the body  An animal model of MS, termed experimental autoimmune encephalomyelitis, can be induced by injecting laboratory animals with myelin and a preparation that stimulates the immune system  Diagnosing MS is difficult because the nature and severity of the disorder depend on a variety of factors including the number, size and position of the sclerotic lesions  Some cases there are periods of remission (up to 2 years), during which the patient seems almost normal; however, these are usually just oases in the progression of the disorder, which eventually becomes continuous and severe  Common symptoms = visual disturbances, muscular weakness, numbness, tremor, and ataxia  Cognitive deficits and emotional changes occur in some patients  Epidemiology is the study of the various factors, such as diet, geographic location, age, sex, and race that influence the distribution of a disease in the general pop  Three epidemiological findings that implicate genetic factors in the etiology of MS o Higher concordance rate in monozygotic (25%) than in dizygotic (5%) twins, o Three times higher incidence in females than in males o Substantially higher incidence in Caucasians (0.15%) than in other ethnic groups, such as native Asians and Africans  Three findings that implicate the environmental factors: o Incidence is higher among pops living in colder climates, as opposed to near the equator Downloaded by Marianne Audrey Pinili ([email protected])  lOMoARcPSD|43883818 o Indis who migrate from a high incidence region to a low incidence region. Particularly at a young age, reduce their susceptibility (and vice versa) o Cigarette smokers are at greater risk  The incidence of MS is highest in regions far from the equator, which are exposed to little strong sunshine, a major source of Vit D o Vit D has been shown to influence a chromosomal locus implicated in multiple sclerosis Alzheimer’s Disease  If the most common cause of dementia  As young as 40  Is progressive  Early stages are often characterized by a selective decline in memory, deficits in attention. And personality changes  Intermediate stages are marked by confusion, irritability, anxiety, and deterioration of speech  In its advanced stages, the patient deteriorates to the point that even simple response such as swallowing and controlling the bladder are difficult  Is terminal – currently no cure  The two defining characteristics of the disease are neurofibrillary tangles and amyloid plaques  Neurofibrillary tangles are threadlike tangles of protein in the neural cytoplasm, and amyloid plaques are clumps of scar tissue composed of degenerating neurons and a protein called amyloid, which is present in normal brains in only very small amounts  Neurofibrillary tangles, amyloid plaques and neuron loss occur more prevalent in some areas o In medial temporal lobe structures such as the entorhinal cortex, Amygdala, and hippocampus – are involved in various aspects of memory o Also prevalent in the inferior temporal cortex, posterior parietal cortex, and prefrontal cortex – mediate complex cognitive functions  Has major genetic component  The amyloid hypothesis is currently the dominant view – proposes that amyloid plaques are the primary symptom of the disorder and cause all the other symptoms o The main support has come from the genetic analysis of families with early onset alz’s disease o All three different gene mutations that cause early onset influence the synthesis of amyloid o Amyloid has been found to be toxic to neurons that have been artificially maintained in tissue culture  The first efforts to develop treatments focused on the fact that declines in acetylcholine levels o Cholinergic agonists are still sometimes prescribed – have proven ineffective Downloaded by Marianne Audrey Pinili ([email protected])  lOMoARcPSD|43883818  The most promising is the immunotherapeutic approach, which involves administering an amyloid vaccine to reduce plaque deposits o Initially proved effect in test s on transgenic mice o Curtailed because of serious side effects on human patients 10.3 Animal Models of Human Neuropsychological Diseases Kindling Model of Epilepsy  Researcher delivered one mild electrical stimulation per day to rats through implanted amygdalar electrode o No behavioural response to the first few stimulations, but soon each stimulation began to elicit a convulsive response o The first convulsions were mild, involving only a slight tremor of the face o With each subsequent stimulation, however, the elicited convulsions became more generalized, until each convulsion involved the entire body  The progressive development and intensification of convulsions elicited by a series of periodic brain stimulations became known as the kindling phenomenon o One of the first neuroplastic phenomena to be widely studied  Can be produced by the repeated stimulation of many brain sites other than the amygdala, and it can be produced by the repeated application of initially subconvulsive doses of convulsive chemicals  Two warrant emphasis: o The neuroplastic changes underlying kindling are permanent – a subject that has been kindled and then left unstimulated for several months still responds to each low intensity stimulation with a generalized convulsion o Kindling is produced by distributed, as opposed to massed, stimulations – if the intervals between successive stimulations are shorter than an hour or two, it usually requires many more stimulations to kindle a subject, and under normal circumstances, no kindling at all occurs at intervals of less than about 20 minutes  Kindling models epilepsy in two ways o The convulsions elicited in kindled animals are similar in many respects to those observed in some types of human epilepsy o The phenomenon itself is comparable to the epileptogenesis that can follow a head injury: some indis who at first appear to have escaped serious injury after a blow to the head begin to experience convulsions a few weeks later, and these sometimes begin to recur more and more frequently and with greater and greater intensity Downloaded by Marianne Audrey Pinili ([email protected])  lOMoARcPSD|43883818  One interesting and potential important development in the study of kindling is that some researchers have started to use it to model interictal behaviour (behaviour that occurs in epileptics between their seizures)  Some, particularly those who suffer from complex partial seizures, pathological changes in interictal behaviour are more distressing and more difficult to treat than the seizures themselves Transgenic Mouse models of Alzheimer’s disease – the best current animal models of ALz’s disease  Transgenic refers to animals into which genes of another species have been introduced  In this model of Alz – genes that accelerate the synthesis of human amyloid are injected into newly fertilized mouse eggs, which are then injected into a foster mother to develop  When mature, these brains contain many amyloid plaques like those of human alz patients  There are problems: most of these models do not display neurofibrillary tangles, which is a serious problem if neurofibrillary tangles prove to be the primary symptom of Alz disease  A triple transgenic mouse model (three different human genes have been inserted) display both amyloid plaques and neurofibrillary tangles, is currently being tested MPTP Model of Parkinson’s Disease  MPTP from drug addicts case  The brains of nonhuman primates exposed to MPT have cell loss in the substantia nigra similar to that observed in the brains of Parkinson’s patients  Considering that substantia nigra is the major source of the brain’s dopamine, it is not surprising that the level f dopamine is greatly reduced in both the MPTP model and in the naturally occurring disorder  It was discovered that deprenyl, a monoamine agonist, blocks the effects of MPTP in an animal model, and it was subsequently shown that deprenyl administered to early Parkinson’s patients retards the progression of the disease 10.4 Neuroplastic Responses to Nervous system damage: Degeneration, Regeneration, Reorganization and Recovery Neural Degeneration  Is a common component of both brain development and disease  A method for the controlled study of this is to cut the axons of neurons  Two kinds of neural degeneration ensue: anterograde degeneration and retrograde degeneration  Anterograde degeneration is the degeneration of the distal segment - the segment of a cut axon between the cut and the synaptic terminals o Occurs quickly following axotomy, because the cut separates the distal segment of the axon from the cell body, which is the metabolic centre of the neuron Downloaded by Marianne Audrey Pinili ([email protected])  lOMoARcPSD|43883818 o The entire distal segment becomes badly swollen within a few hours, and it breaks into fragments within a few days  Retrograde degeneration is the degeneration of the proximal segment – the segment of a cut axon between the cute and the cell body o It progresses gradually back form the cut to the cell body o In about 2 or 3 days, major changes become apparent in the cell bodies of most axotomized neurons  Early degenerative changes to the cell body suggest that the neuron will ultimately die – usually by apoptosis but sometimes by necrosis or a combination of both  Early regenerative changes indicate that the cell body is involved in a massive synthesis of the proteins that will be used to replace the degenerated axon  But early regenerative changes in the cell body do not guarantee the long term survival of the neuron; if the regenerating axon does not manage to make synaptic contact with an appropriate target. The neuron eventually dies  Transneuronal Degeneration – degeneration spreads form damaged neurons to neurons that are linked to them by synapses  Anterograde Transneuronal Degeneration: In some cases transneuronal Degeneration spreads from damaged neurons to the neurons on which they synapse  Retrograde Transneuronal Degeneration: spreads form damaged neurons to the neurons that synapse on them Neural Regeneration  The regrowth of damaged neurons – does not proceed as successfully in mammals and other higher vertebrates as t does in most invertebrates and lower vertebrates  Regeneration is virtually nonexistent in the CNS of adult mammals, and is at best a hit or miss affair in the PNS  In the mammalian PNS, regrowth from the proximal stump of a damaged nerve usually begins 2 or 3 days after axonal damage  What happens next depends on the nature of the injury – there are three possibilities o If the original Schwann cell myelin sheaths remain intact, the regenerating peripheral axons grow through them to their original targets at a rate of a few millimeters per day o If the peripheral nerve is served and the cut ends become separated by a few millimeters, regenerating axon tips often grow into incorrect sheaths and are guided by them to incorrect destinations; that is why it is often difficult to regain the coordinated use of a limb affected by nerve damage even if there has been substantial regeneration Downloaded by Marianne Audrey Pinili ([email protected])  lOMoARcPSD|43883818 o If the cut ends of a severed mammalian peripheral nerve become widely separated or if a lengthy section of the nerve is damaged, there may be no meaningful regeneration at all; regenerating axon tops grow in a tangled mass around the proximal stump, and the neurons ultimately die  Some CNS neurons are capable of regeneration if they are transplanted to the PNS, whereas some PNS neurons are not capable of regeneration if they are transplanted to the CNS o There is something about the environment of the PNS that promotes regeneration and something about the environment of the CNS that does not o Schwann cells, which myelinate PNS axons, clear the debris resulting from neural degeneration and promote regeneration in the mammalian PNS by producing both neurotropic factors and cell adhesion molecules (CAMs) o The neurotrophic factors released by S cells stimulate the growth of new axons, and the cell adhesion molecules on the cell membrane of Schwann cells mark the paths along which regenerating PNS axons grow o In contrast, oligodendroglia, which myelinate CNS axons, do not clear debris or stimulate or guide regeneration  Tend to survive for long periods of time after nerve damage, thus chronically inhibiting regeneration of the axons  When an axon degenerates, axons branches grow out from adjacent healthy axons and synapse at the sites vacated by the degenerating axons, this is called collateral sprouting o May grow out of the axon terminal branches or the nodes of Ranvier on adjacent neurons  In lower vertebrates is extremely accurate – it is accurate in both the CNS and the PNS, and it is accurate even when the regenerating axons do not grow into remnant S cell myelin sheaths  This offers hope of a medical breakthrough: Neural Reorganization Cortical reorganization following damage in lab animals  Sensory and motor cortex are ideally suited to the study of neural reorganization because of their topographic layout  The damage induced reorganization of the primary sensory and motor cortex has been studied under two conditions: following damage to peripheral nerves and following damage to the cortical areas themselves  Kaas et al assed the effect of marking a small lesion in one retina and removing the other o Several moths after, primary visual cortex neurons that originally had receptive fields in the lesioned area of the retina were found to have receptive fields in the area of the retina next tot eh lesions – this change began within minutes of the lesion Downloaded by Marianne Audrey Pinili ([email protected])  lOMoARcPSD|43883818  Pons et al, mapped the primary somatosensory cortex of monkeys whose contralateral arm sensory neurons had been cut 10 years before – found that the cortical face representation had systematically expanded into the original arm are o The scale of the reorganization was far greater than had been assumed to be possible: the 1 o somatosensory cortex face area had expanded its border by well over a cm, likely as a consequence of the particularly long interval between surgery and testing o Sanes, sunner, and Donoghue transected the motor neurons that controlled the muscles of rats’ vibrissae (whiskers) – a few weeks later, stimulation of the area of motor cortex had elicited vibrissae movement now activated other muscles of the face Cortical Reorganization Following Damage in humans  Research has used brain imaging technology to study the cortices of blind individuals o The findings are consistent with the hypothesis that there is continuous competition for cortical space by functional circuits  Without visual input to the cortex, there is an expansion of auditory and somatosensory cortex, and auditory and somatosensory input is processed in formerly visual areas  There seems to be a functional consequences to this organization: blind volunteers have demonstrated skills superior to those of sighted controls on a variety of auditory and somatosensory tasks Mechanisms of Neural Reorganization  Two kinds of mechanisms o A straightening of existing connections, possibly through release from inhibition.  Two observations: reorganization often occurs too quickly to be explained by neural growth, and rapid reorganization never involves changes of more than 2 mm of cortical surface (direct) o And the establishment of new connections by collateral sprouting  Observation: that the magnitude of long-term reorganization can be too great to be explained by changes in exiting connections (direct) Recovery of Function After Brain Damage  Poorly understood  Difficult to study because there are other compensatory changes that can easily be confused with it o Any improvement in the week or two after damage could reflect a decline in cerebral edema (brain swelling) rather than a recovery from the neural damage itself, and any gradual improvement in the months after damage could reflect learning of new cognitive and behavioural strategies rather than the return of lost functions Downloaded by Marianne Audrey Pinili ([email protected])  lOMoARcPSD|43883818  Cognitive reserve – roughly equivalent to education and intelligence – is thought to play a role in the improvements observed after brain damage that do not result from true recovery of brain function  Observed doctors and neuroscientist with brain damage – saw improvement – suggested that these patients had actually not recovered lost brain function but because their cognitive reserve allowed them to accomplish tasks in alternative ways  Cognitive reserve has also been used to explain why educated ppl are less susceptible to the effects of aging related brain deterioration  Substantial interest in the possibility that adult neurogenesis might contribute to recovery from brain damage o Evidence in favour of this possibility is the finding that stem cells tend to migrate short distances into areas of brain damage in adult laboratory animals o There is no evidence, however, that stem ells can migrate from their sites of genesis in the hippocampus and olfactory bulbs to distant areas of damage in the adult human brain 10.5 Neuroplasticity and the treatment Reducing brain damage by blocking neurodegeneration  Studies have shown that it may be possible to reduce brain damage by blocking neural degeneration in human patients o Study: induced cerebral ischemia in rats by limiting blood flow to the brain has two major effects  Produced damage to the hippocampus, a structure that is particularly susceptible to ischemic damage, and it produced deficits in the rats’ performance in the Morris water maze  The hippocampuses of rats in the experimental group were treated with viruses genetically engineered to release apoptosis inhibitor protein – the apoptosis inhibitor protein reduced both the loss of hippocampal neurons and the deficits in Morris Water maze performance  Nerve Growth Factor – neurochemical that can block the degeneration of damage neurons  Estrogens have been shown to limit or delay neuron death in animal models  These neuroprotective effects of estrogens  explain why several brain disorders are more prevalent in males Promoting Recovery from CNS Damage by promoting regeneration  Researcher transected the spinal cords of rats, thus rendering them paraplegic (paralyzed in the posterior portion of their bodies) o Then transplanted sections of myelinated peripheral nerve across the transection Downloaded by Marianne Audrey Pinili ([email protected])  lOMoARcPSD|43883818 o Result: spinal cord neurons regenerated though the implanted schwann cell myelin sheaths, and the regeneration allowed the rats to regain use of their hindquarters  Similar study involved transplanting olfactory ensheathing cells, are similar so S cells, were selected because the olfactory system is unique in its ability to support continual growth of axons from new PNS neurons into the CNS o Made unilateral lesions in the corticospinal tract of rats, which produced partial paralysis on the same side of the body o Then implanted bridges of olfactory ensheathing cells across the lesion o Axons grow through the lesion, and the motor function of the affected paw was partially restored Promoting Recovery from CNS Damage by Neurotransplantation Transplanting Fetal Tissue –  This approach focused on Parkinson’s disease  Early signs were positive – bilateral transplantation of fetal substantia nigra ells was successful in treating the MPTP monkey model o Fetal substantia nigra transplants survived in the MPTP treated monkeys; the transplanted cells innervated adjacent striatal tissue, released dopamine, and, most importantly, alleviated the severe poverty of movement, tremor, and rigidity produced by the MPTP  Tried in patients: although control patients showed no improvement, the implants survived in the experimental patients and some displayed a modest improvement Transplanting Stem Cells  Once injected, stem cells could develop and replace the damaged neurons or myelin, under guidance from surrounding tissue  McDonald et al injected embryonic neural stem cells into an area of spinal damage of rats o Migrated to different areas around the damaged area, where they developed into mature neurons o Rats became capable of supporting their weight with their hindlimbs and walking, albeit awkwardly Promoting Recovery from CNS damage by Rehabilitative Training Strokes – small strokes produce a core of brain damage, which is often followed by a gradually expanding loss of neural function in the surrounding penumbra  Researchers produced small ischemic lesions in the hand area of the motor cortex of monkeys  Then 5 days later, program of hand training and practice was initiated  During the ensuing 3 or 4 weeks, the monkeys plucked hundreds of tiny food pellets form food wells of different sizes  This practice reduced the expansion of cortical damage into the surrounding penumbra Downloaded by Marianne Audrey Pinili ([email protected])  lOMoARcPSD|43883818  The monkeys that received the rehabilitative training also showed greater recovery in the use of their affected hand  One of the principles that has emerged from the study of neurodevelopment is that neurons seem to be in a competitive situation: they compete with other neurons for synaptic sites and neurotrophins, and the losers die  Constraint induced therapy: rehabilitative program based on this principle, was to tie down the function arm for 2 weeks while the affected arm received intensive training o Performance with the affected arm improved markedly over the 2 weeks, and there was an increase in the area of motor cortex controlling that arm Spinal Injury – treatment like support with harness over a moving treadmill (who cant walk)  The effectiveness of this treatment has been confirmed and extended in human patients and in nonhuman subjects Benefits of Cognitive and Physical Exercise  Indis who are cognitively and physically active are less likely to contract neurological disorder – if they do it would be less severe and recovery better  Enriched environments have been shown to increase dendritic branching, the size and number of dendritic spines, the size of synapses, the rate of adult neurogenesis, and the levels of carious neurotrophic factors Phantom Limbs: Neuroplastic Phenomena  Most amputees continue to experience the limbs that have been amputated  The most striking feature is their reality – their existence is so compelling that a patient may try to jump out of bed onto a nonexistent leg or too left a cup with a nonexistent hand  About half of amputees experience chronic sever pain in their phantom limbs  Pain can occasionally be treated by having the amputee concentrate on open the amputated hand, but often surgical treatments are attempted - typical complaint is that an amputated hand is clenched so tightly that the finger nails are diffing into the palm of the hand Downloaded by Marianne Audrey Pinili ([email protected])