Chapter 10 - Neuroplasticity

Brain Tumors

Tumor is a mass of cells that grow independently of the rest of the body

-20% of tumors in the brain are Meningiomas - tumors that grow between the meninges (three membranes that cover the CNS)

-All meningiomas are Encapsulated Tumors - Grow within their own membrane, allowing for easy identification in a CT scan

-Meningiomas are almost always benign tumors that influence the function of the brain due to pressure exerted on surrounded tissue

Encapsulated tumors that grow on cranial nerve VIII are Acoustic Neuromas (tumors that grow on nerves/tracts)

Infiltrating Tumors

Grow diffusely through surrounding tissues, most brain tumors are infiltrating

-Usually malignant tumors - difficult to remove or destroy them completely and are cancerous tissue

Gliomas - brain tumors developed from glial cells are infiltrating, rapidly growing, and most comon type of malignant brain tumors

Metastatic Tumors

Brain tumors that are from infiltrating cells that are carried to the brain by the bloodstream from other parts of the body

-Many originate as cancers of the lung

Strokes

Sudden onset cerebrovascular disorder that causes brain damage, major cause of neurological dysfunction and leading causer of adult disability

-Common consequences include amnesia, aphasia, psychiatric disorders, dementia, paralysis and comas

Infarct - Area of dead/dying tissue produced by a stroke

Penumbra - Dysfunctional area that surrounds the infarct, may recover or die in the following days after a stroke

-Strokes result from either Cerebral Hemorrhage or Cerebral Ischemia

Cerebral Hemorrhage

Bleeding in the brain, occurs when cerebral blood vessels rupture and seeps into surrounding neural tissue and damages it

-Burst aneurysms are a common cause of intracerebral hemorrhage

Aneurysm - balloon-like dilation that forms in the wall of an artery, where the elasticity of the artery wall is defective

-Can be congenital (present at birth) or due to vascular poisons/infections

Cerebral Ischemia

Disruption of the blood supply to an area of the brain, three main causes are;

1. Thrombosis - A plug (Thrombus) is formed and blocks blood flow at the site of its formation, may be composed of a blood clot, fat, oil, air bubble, tumor cells, etc

2. Embolism - Similar to Thrombosis, except the plug (Embolus) is carried by the blood from a larger vessel (where it was formed) to a smaller one and becomes lodged (a thrombus that has taken a trip)

3. Arteriosclerosis - Walls of blood vessels thicken and the channels narrow (usually due to fat deposits), narrowing can eventually lead to complete blockage of blood vessels

Properties of Ischemia-Induced Brain Damage

1. Takes a while to develop

2. Brain damage does not occur equally in all parts of the brain, certain parts (hippocampus regions) are more susceptible

Glutamate and Ischemia-Induced Brain Damage

Blockage of a blood vessels cause the blood-deprived neurons to become overactive, releasing excess glutamate

-Glutamate overactives glutamate receptors (NMDA particularly) in postsynaptic neurons, causing large numbers of Na+/Ca+ to enter postsynaptic neurons

-Excessive internal concentrations of Na+/Ca+ trigger release of more glutamate and trigger sequence of internal reactions that kill the postsynaptic neuron

Traumatic Brain Injuries (TBI)

Closed-Head TBIs are brain injuries produced by blows that do not penetrate the skull, several types;

1. Contusions - Involve damage to cerebral circulatory system, produces internal hemorrhaging, creating a localized collection of blood (bruising)

• Occur after the brain slams against the inside of the skull, causing injuries to accumulate in the subdural space and distorting the surrounding neural tissue, creating a “puddle” of blood (subdural hematoma)

Contrecoup Injuries

Contusions that occur on the side of the brain opposite the side struck by the blow

-The blow causes the brain to strike the inside of the skull on the other side of the head

Mild TBIs (mTBI)

Disturbance of consciousness following a blow to the head, but no evidence of contusion/structural damage

-Most TBIs are mTBIs

Chronic Traumatic Encephalopathy (CTE)

Is the Demetnia (general intellectual deterioration) and cerebral scarring observed in individuals who have experienced repeated mTBIs

Encephalitis

Inflammation of the brain as a result of a brain infection, two types of brain infections;

1. Bacterial Infections - often lead to cerebral abscesses (pockets of pus in the brain) and a major cause of meiningitis (inflammation of the meninges)

• Syphilis is a major cause of brain infections, infecting bacteria are dormant for years then attack multiple parts of the body (including the brain), resulting in mental illness and dementia (general paresis)

2. Viral Infections - Two types, those that have particular affinity for neural tissue and those that attack neural tissue but do not have a greater affinity

• Rabies has a particular affinitiy for neural tissue, causes a fit of rage increasing chance of it being spread

• mumps and herpes attack the nervous system, but have no special affinity

Neurotoxins

Toxic Psychosis - Chronic mental illness produced by a neurotoxin (many heavy metals like Mercury and Lead can produce this)

-Some neurotoxins are endogenous (produced by a person’s own body) such as antibodies that attack parts of the nervous system

-Stress hormones (like cortisol) also have neurotoxic effects

-Glutamate during an ischemic stroke is also classified as a neurotoxin

Genetic Factors

-gene that encode for disorders are rarely dominant since they tend to be quickly eliminated from the gene pool

Down Syndrome - Extra chromosome is created in the egg, resulting in three chromosome 21s rather than two in the zygote

-Consequences range from intellectual disability, early-onset Alzheimer’s disease, and other medical complications

Apoptosis

Apoptosis plays a critical role in early development by eliminating extra neurons, but also plays a role in brain damage

-All six causes of brain damage (tumors, cerebrovascular disorders, closed-head TBIs, infections, toxins and genetic factors) produce neural damage by activating apoptotic programs

Epilepsy

Neurological disorder, characterized by spontaneously recurring seizures

-Applied to patients whose seizures are repeatedly generated due to their own chronic brain dysfunction

-Seizures can take the form of convulsions (motor seizures, involving tremors/rigidity, loss of balance/consciousness) or subtle changes of thought, mood, and behaviour

Causes of Epilepsy

Range from viruses, neurotoxins, tumors and TBIs, as well as 30 different faulty genes and epigenetic mechanisms

-Many cases are associated with faults at inhibitory synapses (GABAergic synapses) that are responsible for preventing excessive excitatory activity in teh brain

-Dysfunctional activity in astrocytes is also implicated in the development of seizures

-Inflammatory processes too

Diagnosis of Epilepsy

Based on scalp EEGs, where the onset of epilepsy is associated with bursts of high-amplitude EEG spikes

-Some individuals also experience psychological changes called Epileptic Auras (bad smell, specific thoughts, vague feelings of familiarity, hallucinations, etc)

-After epilepsy is diagnosed, seizures are categorized as being Focal Seizures or Generalized Seizures

Focal Seizure

Seizure not involving the brain, epileptic neurons at a focus discharge together in bursts; synchronous firing produces the epileptic spike in the EEG

-Tends to spread into the brain regions, but not into the entire brain

Simple Seizures - Focal seizures whose symptoms are primarily sensory, or motor, or both

-Involve only one sort of sensory or motor symptom, rarely accompanied by loss of consciousness

Complex Seizures - Often begin in teh temporal lobe, usually doesn’t spread

-Experiences automatisms (compulsive, repetitive, simple behaviours)

Generalized Seizures

Involve the entire brain, sometimes beginning as focal discharges that gradually spread, or discharges begin almost simultaneously in all parts of the brain

Tonic-Clonic Seizure - Loss of consciousness, loss of equilibrium and violent tonic-clonic convulsions (involves the tonus and clonus)

-Tongue biting, urinary incontinence, cyanosis (turning blue due to lack of oxygen) and hypoxia (shortage of oxygen supply to tissue) which can result in brain damage

Absence Seizure - Primary behaviour symptom is loss of consciousness associated with cessation of ongoing behaviour, vacant look, fluttering eyelids

-EEG is bilaterally symmetrical, common in children and cease at puberty

Epilepsy Treatment

No cure, but frequency/severity can be reduced by anticonvulsant medicine

-Stimulation of the vagus nerve, TMS, and ketogenic diet (high levels of fat, moderate levels of protein, and low levels of carbohydrates)

Parkinson’s Disease

Movement disorder associated with degeneration of dopaminergic neurons in the substantia nigra

-Common symptoms are pronounced tremors during inactivity, muscular rigidity, difficulty/slowness of movement, masklike face

-Variety of “causes”; faulty DNA, brain infections, strokes, tumors, TBIs, neurotoxins

Likely a result of interactions between multiple genetic and environmental factors

Degeneration in Parkinson’s Disease

Severe degeneration in the substantia nigra, midbrain nucleus that projects neurons via the nigrostriatal pathway towards the Striatum of the Basal Ganglia

-Little dopamine in the substantia nigra and striatum in Parkinson’s Patients, instead clumps of Alpha-synuclein (a protein) are found in surviving dopaminergic neurons of the Substantia Nigra

Deep Brain Stimulation and Parkinson’s Disease

Applying low-intensity electrical stimulation continually to a particular area of the brain through stereotaxically implanted electrodes

-Involves chronic bilateral stimulation of the Sbbthalamic Nucleus (lies just beneath the thalamus, richly connected to the Basal Ganglia)

-Symptoms are alleviated within seconds but improvement dissipate quickly when turned off

Huntington’s Disease

Progressive terminal disorder of motor and intellectual function that is produced in adulthood by a dominant gene

-Begins with rapid, complex jerky movements of entire limbs and psychiatric/cognitive deficits

-Cognitive/motor deterioration is so severe, loss of control feeding, bowel movement and recognition of family/friends

Cause of Huntington’s Disease

The gene Huntingtin which codes for the protein Huntingtin Protein leads to accumulation of clumps of the protein within cells which are toxic

-Severe clumping in cells in the straitum, results in cell death destroying connections between straitum and cortex

Multiple Sclerosis (MS)

Progressive disease that attacks the myelin of axons in the CNS

-Symptoms appear in early adulthood, microscopic areas of degeneration on myelin sheaths provided by oligodendroglia

-Myelin damage is so severe, associated axons become dysfunctional and degenerate

-Driven by an interaction between immune-system reactivity and neural degeneration

-Lack of remyelination (generation of new myelins heaths) and generation of new oligodendroglia

Diagnosing MS

Done via MRI, focuses on identifying time course of development of white-matter lsions

-Complex due to nature/severity of MS lesions (number, size, and location)

Progression/Treatment of MS

Periods of remission (up to 2 years) with no symptoms, but eventually becomes severe

-Symptoms include muscular weakness, numbness, tremor, ataxia (loss of motor coordination), cognitive deficits and emotional changes

-Immunomodulatory drugs are used but have minor effects on MS patients, new drugs are focusing on developing remyelination

Risk Factors for MS

Higher in females, Caucasians, and those who’ve lived in cold climates during their childhood

-Vitamin D deficiency, exposure to Epstein-Barr virus and cigarette smoking are more established risk factors

Alzheimers Disease

Most common cause of Dementia, contains three defining characteristics; neurofibrillary tangles, amyloid plaques and neuron loss

Stages of Alzheimers

1. Preclinical - pathological changes in the brain without behaviour/cognitive symptoms

2. Predromal - Mild cognitive impairment, serves as an indicator of Alzheimer’s disease

3. Dementia - Initially a progressive decline in memory, deficits in attention and personality changes, followed by marked confusion, anxiety, deterioration of speech and irritability and finally lack of simple responses (Swallowing, Bladder control)

Defining Characteristics of Alzheimer’s Disease

Neurofibrillary Tangles - threadlike tangles of Tau Protein in the neural cytoplasm

-Tau proteins plays a role in maintain overall structure of neurons

-Particularly prevalent in medial temporal lobe structures (entorhinal cortex, amygdala, hippocampus)

Amyloid Plaques - Clumps of scar tissue composed of dengerating neurons and aggregats of another protein (Beta Amyloids) which is present in healthy brains in small amounts

Neuron Loss

Genetic Factor in Alzheimer’s Disease

Encoding of the protein APOE4 by the APOE gene

-APOE binds to beta-amyloid and that such binding reduces beta-amyloid clearance from the brain and it increases beta-amyloid clumping leading to the development of amyloid plaques

Amyloid Hypothesis

Proposes that amyloid plaques are the primary symptom of the disorder (plaques therefore cause all other symptoms)

-Based on evidence that all four gene mutations influence the synthesis of beta-amyloid and that production of neurofibrillary tangles is downstream from alterations to beta-amyloid

Pathogenic Spread Hypothesis

Proposes that many neurodegenerative diseases (alzheimer’s disease, parkinsons’ disease) result from presence of misfolded proteins that initiate a chain reaction, causing other proteins to misfold

Kindling Model of Epilepsy

Goddard, McIntyre and Leech

-Delivered one mild electrical stimulation to rats per day via implanted amygdala electrode

-Soon, each stimulation elicited a convulsive response that started off as mild, but become more generalized and eventually involved the whole body after subsequence stimulations

Models epilepsy in two ways;

1. Convulsions elicited are similar to those observed in humans with epilepsy

2. Kindling phenomenon is comparable to epileptogenic (development/genesis of epilepsy) where individuals who at first have escaped serious injury begin to experience convulsions weeks later that become more and more frequent/severe

MPTP Model of Parkinson’s Disease

Nonhuman primates respond to MPTP (a drug) in many ways that humans do

-They display parkinsonian motor symptoms, cell loss in substantia nigra and major reduction in brain dopamine