W2 (W3R) Brain damage and Neurodegeneration

Question 1

Brain damage

Answer 1

Can be caused by injury, disease, stroke.

Question 2

Brain injury

Answer 2

Damage caused by stroke or other injury.

Question 3

Congential brain injury

Answer 3

very early life stage, genetic factor (affecting neurodevelopment) pre-natal or birth related trauma.

Question 4

Aquired brain injury

Answer 4

= during the life-time, induces silly things we do to ourself as a species. Can be either Traumatic or non-traumatic.

Question 5

Non-traumatic Brain injury

Answer 5

inside the skull, no control over, sudden (stroke, tumors, lack of oxygen, infection, hypoxia/anoxia)

Question 6

Traumatic brain injury

Answer 6

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.

Question 7

Stroke

Answer 7

Due to age, linked to heart (blood). FAST (= face, arms, speech, time (critcal factors)).

Question 8

2 main causes for strokes

Answer 8

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

Question 9

Closed head injury

Answer 9

no penetration of the skull
Cerebrospinal flid: normal forces applied to the skul present no problem in part due to this cushion of fluid, damage can be diffuse and widespread.

Question 10

Shock research finding

Answer 10

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.

Question 11

Open head injury

Answer 11

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.

Question 12

Brain disease

Answer 12

Neurodegenerative diseases = Alzheimers, parkinsons, and other brain disease (cancer, epilepsy, infection ect.)

Question 13

Alzheimer’s disease

Answer 13

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)

Question 14

Parkinson’s disease

Answer 14

Specific, mainly attributable to loss of single type of neuron in specific brain region, predominatly motor symptoms.
Symptomatic treatment available, but no cure.

Question 15

parkinson’s disease

how common is it?

Answer 15

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).

Question 16

Symptoms of Parkinson’s disease

Answer 16

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.

Question 17

Parkinson’s and neurotransmitter

Answer 17

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).

Question 18

Frozen addict’s story

Answer 18

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

Question 19

Understand the MPTP animal model of Parkinson’s disease.

Answer 19

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.

Question 20

Replacement of lost dopamine ) Parkinsons

Answer 20

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)

Question 21

Surgical intervatin = Parkinsons: lesion

Answer 21

• Surgical approaches = Lesion – surgically damage the problem [output] structures of the basal ganglia. (only in very severe cases) = can be controlled and regulated.

Question 22

Surgical interventions: parkinsons: electrical stimulation

Answer 22

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.

Question 23

Surgical approaches: Parkinson’s: Replace lost DA cells?

Answer 23

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

Question 24

Dementia

Answer 24

“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.”

Question 25

Alzheimer’s Disease

Answer 25

disease causes dementia. Alzheimer’s accounts for most (approx. 2/3) cases of dementia, but there are other types of dementia too = Vascular dementia, Dementia with Lewy bodies, Frontotemporal dementia, Mild cognitive impairment, Posterior cortical atrophy, Primary progressive aphasia.

Question 26

Alzheimer symptomes

Answer 26

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

Question 27

Amyloid Plaques (alzeihmers)

Answer 27

(driving the disease) = Amyloid means “starch” but it is actually a protein. Plaques are aggregate lumps of amyloid proteins (Aβ – beta amyloid).

Question 28

genetic risk factors (Alzeihmers)

Answer 28

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.

Question 29

Neurofibrillary tangles = Tau (Alz)

Answer 29

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.

Question 30

Apolipoprotein E (apoE) Alz

Genetic risk factor

Answer 30

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

Question 31

Animal model

Alzheimer’s

Answer 31

help us dev/understand treatments
Models: genetic modification leads to excessive APP, TAU, or copies of genes coding for the apoE E4 allele.

Question 32

Acetylcholine

Answer 32

= cholinergic system important for normal cognitive function, especially memory

Question 33

Cholinesterase

Answer 33

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

Question 34

Alzheimer’s Treatments

Answer 34

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

Question 35

Brain tumors

Answer 35

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.

Question 36

Meningiomas tumors

Answer 36

grow between the meninges, three membranes that cover the central nervous system).

Question 37

Encapsulated tumors

Answer 37

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)

Question 38

Infiltrating tumors (main)

Answer 38

grow diffusely through surroudnign tissue, as a result they are usually malignant tumors, difficult to remove or destroy.

Question 39

Gliomas: brain tumors

Answer 39

develop from glial cells, they are infiltrating, rapidly growing and unfortunately the most common form of malignant brain tumor.

Question 40

Cerebral ischemia (strokes)

Answer 40

is a disruption of the blood supply to an area of the brain, the main causes are thrombosis, embolism and arteriosclerosis

Question 41

Cerebral hemorrhage (strokes)

Answer 41

bleeding in the brain occurs when a cerebral blood vessel ruptures and blood seeps into surrounding neural tissue and damages it.

Question 42

Cerebrovascular disorders: Strokes

Answer 42

Symptoms depend on the brain area affected. Common consequences of strokes: amnesia, aphasia, psychiatric disorder, dementia, paralysis and coma.
Infract: the area of dead or dying tissue produced by a stroke. Penumbra: is a dysfunctional area surrounding the infarct. The primary goal of treatment is to save the penumbra.

Question 43

Cerebral ischemia causes: Thrombosis

Answer 43

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.

Question 44

Cerebral ischemia causes: Embolism

Answer 44

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.

Question 45

Cerebral ichemia causes: Arteriosclerosis

Answer 45

walls of blood vessels thicken and the channels narrow, usually as a result of fat deposits, the narrowing can lead to complete blockage.

Question 46

Traumatic closed head injuries: Contusions

Answer 46

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.

Question 47

Traumatic closed injuries; contrecoup

Answer 47

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

Question 48

Mild TBI

Answer 48

a disturbance of consciousness following a blow to the head and there is no evidence of a contusion or other structural damage.

Question 49

Chronic traumatic encephalopathy, CTE

Answer 49

is the dementia and cerebral scarring often observed in boxers, rugby players.

Question 50

Brain infection

Answer 50

: is an invasion of the brain microorganisms, and the resulting inflammation is called encephalitis.

Question 51

Brain bacterial infections

Answer 51

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

Question 52

Syphilis

Answer 52

one bacterial brain infection passed from infected to noninfected individuals through contact with genital sores, the bacteria then go into a dormant stage of several years before they become virulent and attack many parts of the body, including the brain.

Question 53

Viral infections

Answer 53

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.

Question 54

Rabies

Answer 54

transmitted through the bite fo a rabid animal virus that has a particular affinity for the nervous system.

Question 55

Mumps and herpes virus

Answer 55

are common examples of viruses that can attack the nervous system but have no special affinity for it.

Question 56

Down syndrome (genetic brain damage)

Answer 56

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.

Question 57

Neurotoxins

Answer 57

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.

Question 58

Epilepsy

Answer 58

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.

Question 59

Huntington’s disease

Answer 59

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.

Question 60

Alzheimer’s disease

Answer 60

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.

Question 61

Gliomas

Answer 61

Brain tumors that develop from glial cells. They are infiltrating rapidly growing and unfortunately the most common form of malignant brain tumors.