W2 (W3R) Brain damage and Neurodegeneration Flashcards
Brain damage
Can be caused by injury, disease, stroke.
Brain injury
Damage caused by stroke or other injury.
Congential brain injury
very early life stage, genetic factor (affecting neurodevelopment) pre-natal or birth related trauma.
Aquired brain injury
= during the life-time, induces silly things we do to ourself as a species. Can be either Traumatic or non-traumatic.
Non-traumatic Brain injury
inside the skull, no control over, sudden (stroke, tumors, lack of oxygen, infection, hypoxia/anoxia)
Traumatic brain injury
Intracranial Injury
Sudden and bad
Specific in focus or widespread.
Can affect brain tissue directly or indirectly be damaging the blood supply (circulatory) system.
Closed or open head injury.
Stroke
Due to age, linked to heart (blood). FAST (= face, arms, speech, time (critcal factors)).
2 main causes for strokes
Cerebral haemorrhage = burst of blood vestle, leaks into brain, loss of blood supply + blood is toxic to brain (neural) tissue.
Cerebral ischaemia = lack of blood sypply, blockage, break blood clot down with drugs. Lack of oxygen/glucose leads to excitotoxicity and neuronal cell death
Closed head injury
no penetration of the skull
Cerebrospinal flid- Closed head injury
normal forces applied to the skul present no problem in part due to this cushion of fluid, damage can be diffuse and widespread.
Shock research finding
repeated powerful blows to the head are not usefull to long term brain health.
Cumulative strucutural damage occurs resulting in dementia symptoms. Some evidence that it leads to increased likelihood of neurodegenerative diseases such as PD and AD.
Open head injury
when the skull doesn’t remain intact.
Objects penetrating the skull and entering the brain. Also damage to the skull such that bone fragments damage brain tissue. Damage can be localised, but risk of other complications (bleeding, infection, swelling) that can lead to wider damage.
Brain disease
NDD
Neurodegenerative diseases = Alzheimers, parkinsons, and other brain disease (cancer, epilepsy, infection ect.)
Alzheimer’s disease
Diffuse changes in brain structure and volume associated with widespread neuronal loss. Predominantly cognitive symptoms in early stages. Associated with loss of the neurotransmitter acetylcholine. Symptomatic treatment available, but no cure. (slow down the rate if early on)
Parkinson’s disease
Specific, mainly attributable to loss of single type of neuron in specific brain region, predominatly motor symptoms.
Symptomatic treatment available, but no cure.
parkinson’s disease
how common is it?
Most common in men.
Associated with Parkinson’s = some genetic mutation + spontaneous factors or environmental factors.
= Affects 0.5% of the population (1-2% of the elderly population)/
Idiopathic disease = which means that each case has its own origins (no single cause).
Symptoms of Parkinson’s disease
Lack of spontaneous movement
Bradykinesia (slow movements)
Akineasia (no moemvents)
Increased muscle tone (rigid)
Resting tremor, shuffling gait and flexed posture, impaired balance.
Even though they struggle to initiate movement they can complete movement.
Parkinson’s and neurotransmitter
Dopamine = Parkinson disease is first example of a brain disorder resulting froma deficiency of a single neurotransmitter. It lacks dopamine in particular pathways (nigrostriatal dopamine pathway found within the basal ganglia).
Frozen addict’s story
Early 80s America, development of new synthetic heroin led to spate of cases of individuals (otherwise young and health) with pronounced Parkinsonian symptoms.
MPTP was an unwanted byproduct of the chemical process, that in the brain becomes converted to the highly neurotoxic MPP+.
Bad bunch of heroin = chemical caused Parkinson’s diseases symptoms
Understand the MPTP animal model of Parkinson’s disease.
MPTP was found to be specifically targeting the dopamine producing cells of the substantia nigra pars compacta. A single injection of a drug that seems to fully and accurately recreate common and complex human disease.
Replacement of lost dopamine ) Parkinsons
Levo Dopa (dopamine precursor)
Apomorphine (dopamine agonist)
Deprenyl (monoamine [dopamine/serotonin] agonist)
Cannabis? A dopamine agonist, seems effective in some cases but overall not backed up by larger scale studies (at least compared to the above)
Surgical intervatin = Parkinsons: lesion
- Surgical approaches = Lesion – surgically damage the problem [output] structures of the basal ganglia. (only in very severe cases) = can be controlled and regulated.
Surgical interventions: parkinsons: electrical stimulation
Electrical stimulation of basal ganglia (Deep brain Stimulation) = Target same sites as lesion but with electrical current tuned to shut them down (inhibit output). [Reversible, controllable/adjustable]. Rapidly becoming more and more affective.
Surgical approaches: Parkinson’s: Replace lost DA cells?
Initial indications of success for fatal/stem cell transplantation have not been underpinned in larger, longer-term trials, at least in terms of balancing risks
Dementia
“a chronic or persistent disorder of the mental processes caused by brain disease or injury and marked by memory disorders, personality changes, and impaired reasoning.”
Alzheimer’s Disease
dementia
Disease causes dementia. Alzheimer’s accounts for most (approx. 2/3) cases of dementia
Other types of dementia too = Vascular dementia, Dementia with Lewy bodies, Frontotemporal dementia, Mild cognitive impairment, Posterior cortical atrophy, Primary progressive aphasia.
Alzheimer symptomes
percentage
symptomes
stages
10% over 65 years old
35% over 85 years old
Memory Loss
Selective decline in memory
Deficits in attention and personality changes
Intermediate stages: confusion, anxiety, irritability
Final stages: swallowing and bladder control
Amyloid Plaques (alzeihmers)
(driving the disease) = Amyloid means “starch” but it is actually a protein. Plaques are aggregate lumps of amyloid proteins (Aβ – beta amyloid).
genetic risk factors (Alzeihmers)
Found on chromosome 21.Downs Syndrome (trisomy chromosome 21)
150% of normal APP levels.
Develop AD pathology by 40 years old. Genetic forms of AD appear to have an early onset. They are usually mutations in the APP gene.
Neurofibrillary tangles = Tau (Alz)
Neurons have “sticks” in them called microtubules. These are part of the cytoskeleton, keeps a cell’s shape. There are made from MAPs – Microtubule Associated Proteins. Tau gets into a ‘muddle’ and gets tangled up.
Apolipoprotein E (apoE) Alz
Genetic risk factor
Risk or protective factor.3 common alleles: E2(good),E3,E4(bad). In the periphery it is involved in transport of cholesterol.
Risk or Protective factor
Animal model
Alzheimer’s
help us dev/understand treatments
Models: genetic modification leads to excessive APP, TAU, or copies of genes coding for the apoE E4 allele.
Acetylcholine
= cholinergic system important for normal cognitive function, especially memory
Cholinesterase
An enzyme that breaks down the neurotransmitter acetylcholine. In other words, prevents acetylcholine from continuing to act on the neurons (normally a good thing). Inhibit AchE, and you increase (prolong) the effect of acetylcholine on the neurons
Alzheimer’s Treatments
Treatment of Tau, Amyloid or apoE related features of AD remain elusive (but watch this space: immuno- and gene-therapy approaches)
Treatment instead targets an additional simultaneous pathological feature of AD: Loss of neurons that produce/release the neurotransmitter acetylcholine
Brain tumors
A tumor or neoplasm is a mass of cells that grows independently of the rest of the body. About 20% of tumors found in the human brain are meningiomas (all are encapsulated). Most tumors are Infiltrating tumors.
Meningiomas tumors
grow between the meninges, three membranes that cover the central nervous system).
Encapsulated tumors
tumors that grow within their own membrane, easy to identify on CT can, they can influence the function of the brain only by the pressure they exert on surrounding tissue, they are usaly surgically removable with little risk (benign tumors)
Infiltrating tumors (main)
grow diffusely through surroudnign tissue, as a result they are usually malignant tumors, difficult to remove or destroy.
Gliomas: brain tumors
develop from glial cells, they are infiltrating, rapidly growing and unfortunately the most common form of malignant brain tumor.
Cerebral ischemia (strokes)
is a disruption of the blood supply to an area of the brain, the main causes are thrombosis, embolism and arteriosclerosis
Cerebral hemorrhage (strokes)
bleeding in the brain occurs when a cerebral blood vessel ruptures and blood seeps into surrounding neural tissue and damages it.
Stroke (symptoms/consequences)
Symptoms depend on the brain area affected. Common consequences of strokes: amnesia, aphasia, psychiatric disorder, dementia, paralysis and coma.
Cerebral ischemia causes: Thrombosis
plug called a thrombus is formed ad blocks blood flow at the site of its formation, may be composed by blood clot, fact, iol, air, bubble, tumor cells ect.
Cerebral ischemia causes: Embolism
the plug called embolus is carried by the blood from a larger vessel where it is formed to a smaller one where it becomes lodge.
Cerebral ichemia causes: Arteriosclerosis
walls of blood vessels thicken and the channels narrow, usually as a result of fat deposits, the narrowing can lead to complete blockage.
Traumatic closed head injuries: Contusions
closed head TBIs that involve damage to the cerebral circulatory system. Such as damage produces internal hemorrhaging which in turn produces a localized collection of blood in the brain, a bruised brain. Blood can accumulate in the subdural space (between dura mater and arachnoid membrane): subdural hematoma.
Traumatic closed injuries; contrecoup
the blow causes the brain to strike the inside of the skull on the other side of the head.
Mild TBI
a disturbance of consciousness following a blow to the head and there is no evidence of a contusion or other structural damage.
Chronic traumatic encephalopathy, CTE
is the dementia and cerebral scarring often observed in boxers, rugby players.
Brain infection
: is an invasion of the brain microorganisms, and the resulting inflammation is called encephalitis.
Brain bacterial infections
when they infect the brain they lead to the formation of cerebral abscesses, pockets of puss in the brain. Bacteria are also the major cause of meningitis (inflammation of the meninges), which is fatal in 30% of adults
Syphilis
Bacterial brain infection passed from infected to noninfected: STD
the bacteria => dormant stage => virulent and attack many parts of the body, including the brain.
Viral infections
two types of viral infections of the nervous system; those that have a particular affinity for neural tissue and those that attack neural tissue but have no greater affinity for it than other tissues.
Rabies
transmitted through the bite fo a rabid animal virus that has a particular affinity for the nervous system.
Mumps and herpes virus
are common examples of viruses that can attack the nervous system but have no special affinity for it.
Down syndrome (genetic brain damage)
occurs during ovulation when an extra chromosome 21 is created in the egg. He consequences tend to be characteristic disfigurement intellectual disability, early onset Alzheimer’s disease and other troublesome medical complications.
Neurotoxins
The nervous system can be damaged by exposure to any one of a variety of toxic chemicals, enter from the gastrointestinal tract, lung or skin. Some neurotoxins are endogenous (produced by the patient’s own body), body can produce antibodies that attack particular components of the nervous system. Stress hormones (cortisol) also are believed to produce neurotoxic effects.
Epilepsy
Seizures that take the form of convulsions (motor seizures); these often involve tremors ( clonus ), rigidity ( tonus ), and loss of both balance and consciousness. But most seizures do not take this form; instead, they involve subtle changes of thought, mood, or behavior that are not easily distinguishable from normal ongoing activity.
Huntington’s disease
Huntington’s disease is a rare genetic disorder that causes progressive motor and cognitive decline. It is inherited through a single mutated gene called huntingtin, which leads to the production of the huntingtin protein.
Alzheimer’s disease
stages
3 stages:
Preclinical stage ( pathological changes in the brain without any behavioral or cognitive symptoms)
Prodromal stage: mild cognitive impairment.
Dementia stage, progressive decline of memory, deficits in attention, personality changes, followed by marked confusion, irritability, anxiety, deterioration of speech.
Gliomas
Brain tumors that develop from glial cells. They are infiltrating rapidly growing and unfortunately the most common form of malignant brain tumors.
Infract - Strokes
nfract: the area of dead or dying tissue produced by a stroke.
Penumbra - Strokes
is a dysfunctional area surrounding the infarct. The primary goal of treatment is to save the penumbra.
