Trigger 7: Microglia

Question 1

TBI results in neuroinflammation which include activation of

Answer 1

local ramified microglia- amoeboid shape- which leads to the production of inflammatory cytokines

Question 2

which substances leak out of the brain during TBI

Answer 2

a huge efflux of …

glutamate
chloride
potassium and sodium

Question 3

swelling and inflammation from tissue damage

Answer 3

increase the pressure, producing more damage

Question 4

when swelling and inflammation from tissue damage occurs

Answer 4

♣ a craniotomy is performed to prevent pressure cuaisng more damage
♣ NO KNOWN DRUG WHICH STOPS THIS
♣ No treatment which stops leakage of NT

Question 5

positives of inflammation

Answer 5

necessary for clearance of harmful substance (cell debris) after TBI

Question 6

negatives of inflammation

Answer 6

contributes to brain injury following TBI

Question 7

microglia are the

Answer 7

resident macrophages of the brain- helping to maintain homeostasis by removing debris and toxic substances

Question 8

after trauma

Answer 8

microglia are activated promptly morning into a motile amoeboid state and migrating to damage regions

Question 9

microglia have been found to have two polarisation states

Answer 9

M1 and M2

Question 10

M1 activated by

Answer 10

LPS, IFN-Y, TNF-a

Question 11

M1 release

Answer 11

TNF-a, IFN-y, iNOS, IL-1B, IL-6

Question 12

M2 activated by

Answer 12

IL4, IL-13, IL-10, TGF-B

Question 13

M2 release

Answer 13

TGF-B, arginase 1, Ym1, FIZZi, IL-10

Question 14

M2 play a role in

Answer 14

• resolution of neuroinflamamtion
• clearance of debris
• CNS remodelling and neuronal repair
• neurogenesis and angiogenesis

Question 15

oligodendrocyte differentiation

Answer 15

demyelination

Question 16

microgliosis

Answer 16

Where microglia in a resting state become activated. - –Microglial cells are the primary initiators of the central inflammatory response to acute and chronic disorders.

Question 17

outline microliosis process

Answer 17

1) ramified microglia carrying out immune surveillance
2) TBI injury
3) activation of microglia –> M1 and M2
4) if resolved microglia return to resting state
4) if unresolved the microglia become primed with increased MHCII and CD68
5) microglia become hyperacitvation e.g. by immune challenge
6) release of inflammatory markers

Question 18

M1 can lead the production of

Answer 18

free radical generation

Question 19

free radicals cause

Answer 19

mitochondrial dysfunction–> accelerated excitotoxicity and synaptic dysfunction
–> immunoexcitoxicity

Question 20

astrogliosis

Answer 20

Astrogliosisis an abnormal increase in the number of astrocytes due to the destruction of nearby neurons from CNS trauma, infection, ischemia, stroke, autoimmune responses, and neurodegenerative disease

Question 21

result of astrogliosis

Answer 21

glial scar formation

Question 22

astorgliosis process

Answer 22

1) healthy astrocyte activated due to TBI/ insult
2) astrocyte becomes a reactive astrocyte (proliferate and migrate
3) which are recruited to the site of injury
4) goal scar

Question 23

the scar secretes

Answer 23

neuro-developmental inhibitor molecules - preventing couple physical and functional recovery of the CNS after insult

Question 24

intracellular molecular cascade by astrogliosis

Answer 24

look at notes

Question 25

histopathological events of TBI

Answer 25

1) mechanical CNS damage
2) immune cell invasion
3) astrocytic scar formation
4) structural reorganisation

Question 26

when are m2-like microglia activated

Answer 26

within hours

Question 27

m1 microglia activation occurs

Answer 27

after M2-like activation

Question 28

when do neutrophils join the immune response

Answer 28

first line responder (within hours)

Question 29

when does T cell infiltration occur

Answer 29

within dayss

Question 30

when does the cytokine/ chemokine storm start and when is it at its peak

Answer 30

within the first few hours

Question 31

summary of immune response to TBI

Answer 31

1) BBB disruption
2) microglial activation (first M2 then M1
3) immune cell infiltration
4) regeneration and glial scar formation
5) neurogenesis

Question 32

M2 phenotypes increase

Answer 32

• anti-inflammatory cytokines
• phagocytosis secretion
• neutrophil factors

Question 33

M1 phenotypes increase

Answer 33

• pro-inflamamtory cytokines
• chemokine
• ROS