Trigger 7: polarization state of microglia in TBI Flashcards
M1 and M2
are the polarised state of microglia
patrolling microglia (ramified)
Survey for homeostasis disruption
- phagocytosis
- neurogenesis regulation
- synapses remodelling
what trigger the activation of an M1 state
LPS
IFNy
IL-17
TNF-alpha
what trigger the activation of an M2 state
IL-4
IL-10
IL-13
TGF-B
M1
pro-inflammatory phenotype- neurotoxic
M2
anti-inflammatory phenotypes - neuroprotective
M1 causes
cell death and neurotoxicity
- chronic neuroifnlamamtion
- oxidative stress
- immune cell infiltration
- neuronal damage
what do M1 release
iNOS
TNF-alpha
IL-6
IL-1B
which cytokines released by M1 stimulate M2
IL-4 and IL-13
M2 causes
anti-inflammatory neuroprotective response
- increase resolution of inflammation
- restoring homeostasis
which cytokines do M2 release
Arginase-1
TGF-B
Ym-1
FIZZI
name the anti inflammatory microglia
M0 M2a M2b M2c
name the inflammatory microglia
M1
name the wound healing angiogenesis microglia
M2d
what are disease associated microglia
a new protective microglia found in people with ALS- surround area of insult (e.g. plaque deposition) and secrete anti-inflammatory cytokines to prevent further damage
DAM
disease associated microglia
DAM simple
secrete anti-inflammatory cytokines to prevent further damage
activation receptors for M1 activaton
LPS, IFNY, GM-CSF
activation receptors for M2 activation
IL-4, IgG, IL-10
upregulated …. and …… increase risk of of neurodegeneration
APOE and TREM2
down regulated …. decreased risk of neurodegeneration
BIn1
most common genetic biomarkers for the prediction of vulnerability to TBI (expressed on microglia)
BDNG
APOE
TREM2
BDNF
BDNF allele was previously linked to a higher risk of experiencing mTBI
APOE
association with the potential for memory deficits following mTBI
TREM2
association with the potential for memory deficits following mTBI
ramified microglia…
clear metabolic products and tissue debris
what do ramified microglia have on their surface
PRRs which recognise DAMPs e.g. TLRs
ramified microglia are
APCs- interact with T cells
