Trigger 7: Microglia Flashcards
TBI results in neuroinflammation which include activation of
local ramified microglia- amoeboid shape- which leads to the production of inflammatory cytokines
which substances leak out of the brain during TBI
a huge efflux of …
glutamate
chloride
potassium and sodium
swelling and inflammation from tissue damage
increase the pressure, producing more damage
when swelling and inflammation from tissue damage occurs
♣ a craniotomy is performed to prevent pressure cuaisng more damage
♣ NO KNOWN DRUG WHICH STOPS THIS
♣ No treatment which stops leakage of NT
positives of inflammation
necessary for clearance of harmful substance (cell debris) after TBI
negatives of inflammation
contributes to brain injury following TBI
microglia are the
resident macrophages of the brain- helping to maintain homeostasis by removing debris and toxic substances
after trauma
microglia are activated promptly morning into a motile amoeboid state and migrating to damage regions
microglia have been found to have two polarisation states
M1 and M2
M1 activated by
LPS, IFN-Y, TNF-a
M1 release
TNF-a, IFN-y, iNOS, IL-1B, IL-6
M2 activated by
IL4, IL-13, IL-10, TGF-B
M2 release
TGF-B, arginase 1, Ym1, FIZZi, IL-10
M2 play a role in
- resolution of neuroinflamamtion
- clearance of debris
- CNS remodelling and neuronal repair
- neurogenesis and angiogenesis
oligodendrocyte differentiation
demyelination
microgliosis
Where microglia in a resting state become activated. - –Microglial cells are the primary initiators of the central inflammatory response to acute and chronic disorders.
outline microliosis process
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
M1 can lead the production of
free radical generation
free radicals cause
mitochondrial dysfunction–> accelerated excitotoxicity and synaptic dysfunction
–> immunoexcitoxicity
astrogliosis
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
result of astrogliosis
glial scar formation
astorgliosis process
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
the scar secretes
neuro-developmental inhibitor molecules - preventing couple physical and functional recovery of the CNS after insult
intracellular molecular cascade by astrogliosis
look at notes
histopathological events of TBI
1) mechanical CNS damage
2) immune cell invasion
3) astrocytic scar formation
4) structural reorganisation
when are m2-like microglia activated
within hours
m1 microglia activation occurs
after M2-like activation
when do neutrophils join the immune response
first line responder (within hours)
when does T cell infiltration occur
within dayss
when does the cytokine/ chemokine storm start and when is it at its peak
within the first few hours
summary of immune response to TBI
1) BBB disruption
2) microglial activation (first M2 then M1
3) immune cell infiltration
4) regeneration and glial scar formation
5) neurogenesis
M2 phenotypes increase
- anti-inflammatory cytokines
- phagocytosis secretion
- neutrophil factors
M1 phenotypes increase
- pro-inflamamtory cytokines
- chemokine
- ROS
