Psychobio Chapter 10: Brain Damage and Neuroplasticity

2 types of brain tumors

1. benign

2. malignant

benign tumor

• grow slowly and have distinct borders

• no not invade surrounding tissue

• do not invade other parts of the body

malignant tumor

• can grow quickly and have irregular borders

• often invade surrounding tissue

• can spread to other parts of the body through a process called metastasis

brain tumor

• a tumor (neoplasm) is a mass of cells that grows independently of the rest of the body — a cancer

• most ______ are infiltrating

meningiomas

• 20% of brain tumors are ______ — tumors encased in meninges (dura, pia, arachnoid)

  • encapsulated, growing with their own membranes

  • usually benign, surgically removable

metastatic

• about 10% of brain tumors are ___ (starts in one reign of the body and moves to another) — they originate elsewhere, usually the lungs

glioblastoma multiforme (GBM)

stroke

• a sudden-onset cerebrovascular event that causes brain damage

  • third leading cause of death in the U.S. and most common cause of adult disability

  • two types

    1. cerebral hemorrhage

    2. cerebral ischemia

cerebral hemorrhage

• bleeding in the brain

  • stroke because of aneurysm

aneurysm

• a weakened point in a blood vessel that makes a stroke more likely; may be congenital (present at birth) or due to poison or infection

cerebral ischemia

• disruption of blood supply

  1. thrombosis

  2. embolism

  3. arteriosclerosis

• stroke happens because clot stops blood supply to an area of the brain

  • because of thrombosis

thrombosis

• a plug forms in the brain

  • causes: blood clot

embolism

• a plug forms elsewhere and moves to the brain

arteriosclerosis

• a wall of blood vessels thicken, usually due to fat deposits

damage due to cerebral ischemia

• does not develop immediately

• most damage is consequence of excess neurotransmitter release — especially glutamate

• blood-deprived neurons become overactive and release glutamate

• glutamate over activates its receptors, especially NMDA receptors leadings to an influx of Na+ and Ca2+

  • the release of still more glutamate

  • a sequence of internal reaction that ultimately kill the neuron

• ischemia-induced brain damage:

  • takes time

  • does not occur equally in all parts of the brain

  • mechanisms of damage vary with the brain structure

closed-head injuries

• brain injuries due to blows that do not penetrate the skull — the brain collides with the skull

contrecoup injuries (closed-head injuries)

• contusions are often on the side of the brain opposite to the blow

contusions

• closed-head injuries that involved damage to the cerebral circulatory system — hematoma (bruise) form

concussions

• when there is disturbance of consciousness following a blow to the head and no evidence of structural damage

punch-drunk syndrome

• while there is not apparent brain damage with a single concussion, multiple concussions may result in a dementia

chronic traumatic encephalopathy (CTE)

• is a progressive degenerative disease of the brain found in athletes (and others) with a history of repetitive brain trauma, including symptomatic concussions as well as asymptomatic subconcussive hits to the head

• clinical symptoms include changes in

  • mood (i.e., depression, suicidality, apathy, anxiety)

  • cognition (i.e., memory loss, executive dysfunction)

  • behavior (i.e., short fuse, aggression)

  • motor disturbance (i.e. difficulty with balance and gait)

encephalitis

• resulting inflammation of the brain y an invasion of microorganisms

  • bacterial infection

    • often lead to abscesses, pocket of puss

    • may inflame meanings, creating meningitis

    • treat with penicillin and other antibiotics

  • viral infection: Rabies

    • some preferentially attack neural tissues

    • induced coma therapy (Milwaukee protocol)

Rabies

• some preferentially attack neural tissues

• induced coma therapy (Milwaukee protocol)

• Lewi bodies and other lesions

  • affects substantia nigra neurons

treponema pallidum

• syphilis bacteria

• general paresis can occur between 3-30 yrs after getting pyphilis

  • people with general paresis can have personality or mood changes

• tabes dorsalis can occur 5-50 yrs after initial syphilis infection

  • is characterized by pains in the limbs or abdomen, failure of muscle coordination, and bladder disturbances

    • other signs include vision loss, loss of reflexes and loss of sense of vibration, poor gait, and impaired balance

neurotoxins

• may enter general circulation from the GI tract or lungs, or through the skin

• are endogenous (produced by the body)

  • E.g. auto-immune disorders

toxic psychosis

• chronicle insanity produced by neurotoxin

crack pots

• lead poisoning

  • Based on English tea drinkers were having psychosis but they did not know why until they realized that the tea pots they were using had lead in them giving them poisoning

mad hatter

• mercury poisoning

  • Erethism mercuialis

  • Based on English hat makers who used dye that had mercury to make their hats different colors and because they were touching and exposed to the dye they became psychotic due to the mercury poisoning

tardive dsykinesia

• some antipsychotic drugs produce motor disorders

down syndrome

• Most neurophysiological diseases of genetic origin are associated with recessive genes

  • 0.15% of births, probability increases with advancing maternal age

  • Extra chromosome 21 created during ovulation

  • Characteristic disfigurement, mental retardation, other health problems

  • Used to be named mongolism — their faces looked like the faces of ancient mongolians

neuropsychological disorders

• Epilepsy

• Parkinson’s disease

• Huntington’s disease

• Multiple sclerosis

• Alzheimer’s disease

epilepsy

• Primary symptom is seizures, but not all who have seizures have epilepsy

• Epileptics have seizures generated by their own brain dysfunction

• Affects about 1% of the population

• Difficult to diagnose due to the diversity and complexity of epileptic seizures

  • Some kids grow out of it (ex: Evan)

• Types of seizures

  • Convulsions – motor seizures

  • Some are merely subtle changes of thought, mood, or behavior

• Causes

  • Brain damage

  • Gener – over 70 known so far

  • Faults at inhibitory synapses

  • “Febrile seizure” (spike in body temperature; infection)

• Diagnosis

  • EEG – electroencephalogram

  • Seizures associated with high amplitude spikes

two types of epilepsy:

1. partial

2. generalized

two types of partial epilepsy:

1. simple

2. complex

two types of generalized epilepsy:

1. petit mal

2. grand mal

partial epilepsy

• does not involve the whole brain

generalized epilepsy

• involves the whole brain

simple partial epilepsy

• symptoms are primarily sensory or motor or both (Jacksonian seizures)

  • symptoms spread as epileptic discharge spreads

complex partial epilepsy

• often restricted to the temporal lobes (temporal lob epilepsy)

• patients engages in compulsive and repetitive simple behaviors (automatisms)

  • moving like animatronic (aka a robotic)

petit mal generalized epilepsy

• NOT associated with convulsions

• a disruption of consciousness associated with a cessation of ongoing behavior

grand generalized mal epilepsy

• loss of consciousness and equilibrium

• tonic-clonic convulsions

  • tonic = rigidity

  • clonus = tremors

aura

• preceded after seizures ______ such as smell, hallucination, or feeling

  • ____’s nature suggests the epileptic focus

  • warm epileptic of an impending seizure

Parkinson’s Disease

• a movement disorder of middle and old age effecting about 0.5% of the population

• tremor at rest is the most common symptom of the full-blown disorder

• dementia is not typically seen

• no single cause

• associated with degeneration of substantia nigra; these neurons release dopamine to the striatum of the basal ganglia

• approaches to help with the disease

  • research is being done in stem cell research

  • deep brain stimulation (DBS) reduces some of the symptoms

• Almost no dopamine in the substantia nigra of Parkison’s patients

• Autopsies often reveal Lewy bodies (protein clumps) in the substantia nigra

• Linked with 10 different gene mutation

stem cell research (Parkinson’s)

• Implant young dop neurons to start pumping out dopamine since the dopamines naturally created is dying

• Michael J Fox is advocating for it because he has it

Deep brain stimulation (DBS)

• stimulation of subthalamic nucleus reduces symptoms, but effectiveness slowly declines over months or years

subthalamic nucleus (STN)

• effective for tremor, slowness, rigidity, dystonia, and dyskinesia — most commonly used to treated Parkinsons

thalamus (VIM)

• effective for tremor — it is often used to treat essential tremor

globus pallidus (GPi)

• effective for tremor, slowness, rigidity, dystonia, and dyskinesia — it is used to treated dystonia and Parkinsons

multiple sclerosis (MS)

• A progressive disease that attacks CNS myelin leaving areas of hard scar tissue (sclerosis)

• Nature and severity of deficits vary with the nature, size, sand position, of sclerotic lesion

• Periods of remission are common

• Symptoms include visual disturbances, muscle weakness, numbness, tremor, and loss of motor control (ataxia)

• The myelin sheath covering axon in CNS gets attack by the body's own immune cells

• to treat it:

  • We know that immune cells can be appressed

  • To treat and prevent the aggression you treat the people with immune suppressants

    • Ex: advil, nonsteroidal antiinflammatory drugs

    • Can be alleviated some of the symptoms of MS but by suppressing the immune cells you suppress the immune system and risk getting sick

      • Have to add antibiotics to try and prevent overall sickness/infection and give them some defense

• Epidemiological studies find the incidence of MS is increased in those who spend childhood in a cool climate

• MS is rare among Africans and Asians

• Only some genetic predisposition and only one chromosomal locus linked to MS with any certainty

• Young or old can be afflicted with the disease

biological explanation of MS

• Immune (white blood) cells cannot penetrate the blood brain barrier (BBB)

• The neuron has the axon which has the myelin sheath

  • The glial cells (oligodendrocyte) providing the myelin sheath

• The microglia cells become activate (unsure why) and start attacking the myelin sheath

• Some of the lymphocytes are able to penetrate the BBB and attack the myelin sheath as well

• So multiple sclerosis is considered an autoimmune disease

  

Alzheimer’s Disease

• Most common cause of dementia (loss of memory) — likelihood of developing it increases with age

• Progressive, with early stage characterized by confusion and a selective decline in memory

• Definitive diagnosis only at autopsy — must observe neurofibrillary tangles and amyloid plaques causing the disease

  • Two types of proteins the tau proteins in the tangles and the beta proteins in the plaques

2 types of proteins involved in Alzheimer’s

1. tau proteins

2. beta proteins

general paresis

• can occur between 3-20 yrs after getting syphilis

  • people with _____ can have personality of mood changes

tabes dorsalis

• characterized by pains in the limbs or abdomen, failure of muscle coordination, and bladder disturbances

  • other signs include vision loss, loss of reflexes, loss of sense of vibration, poor gait, and impaired balance

  • ______ can occur anywhere from 5-50 yrs after initial syphilis infection

early signs of Alzheimer’s

• Decline in acetylcholine levels

• loss of smell — before loss memories

  • degeneration of neurons in the olfactory valve

  • saying that they have a test for the sens of smell early on to try and do some early intervention

2 types of Alzheimer’s

• early onset (<65)

• late onset (>65)

early onset Alzheimer’s

• can develop it as early as 40 yrs old

• genes of disease can be found in chromosome 21, 14, 1

  • 21 = associated with down syndrome and often they get this early Alzheimer

    • contains an autosomal dominant gene → APP (amyloid precursor)

    • have 3 21 chromosome so they have extra APP getting pumped out causing Alzheimers

late onset Alzheimer’s

• there are a lot of genes associated with this — that’s why they can’t narrow it down

aducancuman

• Approved by FDA

• Derived of healthy, aged donors who were cognitively norma

• Rationale was that these donors’ immune systems had successfully resisted Alzheimer’s disease and that the operative antibodies could be turned into therapeutics by a process called “reverse translational medicine” bing aggregated forms of Aβ (beta amyloid)

• It stumbled after its launch and is not longer being sold

lecanemab

• Monoclonal antibody consisting of the humanized version of a mouse antibody, mAb158, that recognizes protofibrils and prevents amyloid beta deposition in animal models of Alzheimer's disease

• In a trial that involved 1,795 participants with early-stage, symptomatic Alzheimer’s, lecanemab slowed clinical decline by 27% after 18 months of treatment compared with those who received a placebo

• While lecanemab may be offered in doctors’ offices soon, the price tag, which Eisai reportedly has set at $26,500 per year, may make it unaffordable for most people.

• 45% of participants had treatment-related adverse events, with merely 1 in 4 patients developing brains swelling and/or bleeding

Huntington’s Diseas

• a mutation in the HTT gene

• If parents has ______ gene there is a 50% chance of their child to inherit the gene

  • Around the age of 40 they will start to develop symptoms and die shortly after that

• Their movement looks as if they are “dancing” unable to control their limbs

Kindling model of epilepsy

• Experimentally induced seizure activity

• Kindling phenomenon = a series of periodic brain stimulations eventually elicits convulsions

  • Neural changes are permanent

  • Produced by stimulation distributed over time

  • Phenomenon is comparable to development of epilepsy (epileptogenesis) seen following a head injury

• Convulsions are similar to those seen in some forms of human epilepsy – but they only occur spontaneously if kindled for a very long time

  • Tetanic stimulation (high stimulation) = called this because is similar to the tetanus toxic that also causes convulsions

Kindling phenomenon

• a series of periodic brain stimulations eventually elicits convulsions

  • Neural changes are permanent

  • Produced by stimulation distributed over time

  • Phenomenon is comparable to development of epilepsy (epileptogenesis) seen following a head injury

Transgenic mouse model of Alzheimer’s

• Mice producing human amyloid

• Transgenic = take a gene from one species and transports it into another species

• Only humans and a few related primates develop amyloid plaques

• Genes accelerating human amyloid synthesis introduced in mice

  • Plaque distribution comparable to that in AD

  • Unlike humans, no neurofibrillary tangles

transgenic

• take a gene from one species and transports it into another species

MPTP model of Parkinson’s

• Drug-induced damage comparable to that seen in Parkinson’s

• Use COMT (catechol-O-methyltransferase) drugs that helps to prevent the breakdown of dopamine

• The case of the frozen addicts:

  • Synthetic heroin produced the symptoms of Parkisons’s

  • Contains MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)

  • MPTP causes cell loss in the substantia nigra, like that seen in Parkinson’s

  • Animal studies led to the finding that deprenyl can retard the profession of Parkinson’s (inhibiting the action of the MAO-B)