Stroke and mechanisms of neurodegeneration Flashcards Preview

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Flashcards in Stroke and mechanisms of neurodegeneration Deck (23)
1

How do you confirm pathological cell death?

neuropathology(death by necrosis easily detectible) or MRI

2

5 causes of pathological neurodegeneration

-ageing
-stroke
-2y to disease - diabetes neuropathy, HIV encephalopathy
-neurodegen disease e.g. parkinsons huntingtons
-endog toxins

3

5 necrotic events and 2 apoptotic events that cause nn cell death

prion disorder, free radicals, excessive excitatory receptor activation , HIV , neurotoxic drug insult
mitochondrial damage and no GFs

4

What is excitotoxicity

when depol factors overcome the control of ionic homeostasis --> initiate pathogenesis

5

describe the excitotoxicity cascade

NMDA lets in to much calcium which causes:
-oxidative stress (free rad production)
- calcium dependant enzymes e.g phospholipase (breaks down cell wall) kinase , endonuclease degrade DNA
-damages the mitochondria
causing necrosis and apoptosis

6

describe the two types of NMDA receptors

ionotrophic - ion channel CALCIUM
metabotrophic - g protein

7

when does excitotoxicity occur in epilepsy

after increased neuronal activity a 2nd spread of excitotoxic neuronal death can occur

8

How does noise induce deafness and how can you prevent this

exposing cochlear receptors to beyond withstand causes death of inner and outer nn cells
glutamate antagonist OR interfere apoptotic pathway

9

neuronal death in AIDS

AIDS replicates in microglia. infected microglia presents gp120 on surface to astrocytes which causes both the astrocytes and the microglia to release TNF causing release of glutamate = excitotoxicity

10

what are.. glutathione, ascorbate, vit E, flavanoids

antioxidants

11

descrive how 02 can become pro oxidants

02 --> 02 (-) --> H202 --> H0(-) --> H20
-superoxide anion 02- is removed by superoxide dismutase
-hydrogen peroxide is removed nu reduction to h2- or glutathione
-hydroxyl radicals VERY reactive

12

what is the fenton reaction

h202 --> OH - using Fe2+ or other metals to enable reaction.
means that free iron is very dangerous

13

How can redox stress cause damage - 3

1. lipid peroxidation of fatty acids
2. protein oxidation. can impaire enzymes involved in Ca homeo
3. DNA strand scissors impaired (impaired ATP synthesis )

14

relationship between redox and excitotoxicity

SYNERGISTIC

15

evidence of oxidative stress in parkisons that can be found in a post mortem

increased lipid peroxidation
increaed free rads
increased brain iron
increased superoxide dismutase activity
decreased glutathione

16

what is parkin gene responsible for

degradation of proteins (ubuiqatin proteosome)

17

How does ALS cause neurodegeneration

mutations in superoxide dismutase activity therefor oxadative stress - loss of motorneurones - weakness and muscle atrophy

18

Two types of strokes?

hemorrhagic - 10% bleeding around/in brain
ischemic - 90% clot blocks blood flow to an area

19

what is a blood flow deficit made up of

core + penumbra (compromised area)

20

describe the main early events in a stroke

hypoxia
failure of aerobic metabolism = LACTATE, neurones and glia CANT maintain ion gradient
release glutamate
increased intracellular calcium
cellular oedema brain swelling
increased ICP

21

what happens 1w after a stroke (beneficial)

endogenous neurogenesis

22

what exodogenous therapy can be used after a stroke

GFs may be used to stim proliferation
stem cells from brain implants may be used to start neurogenesis

23

what are the two main aims of stroke therapy and how do you achieve them

rapid restoration of blood flow
-iv TPA removes clots, surgery, brain cooling
encouraging recovery of surviving
- supportive care, physiotherapy