Trigger 7: TBI and cells of the brain Flashcards
name the glial cells of the CNS
astrocytes
microglia
oligodendrites
ependymal cells
name the glial cells of the PNS
satellite cells
schwann cells
two types of glia
PNS and CNS
how much of the brain volume do glia make up
70%
why do glial cells make up 70% of the brain volume
huge amount of cells needed to support neurones
half of all glia are
astrocytes
role of glia cells
- clear out substances that shouldn’t be there - maintaining neurones - maintaining tight junctions
support cells of the CNS
astrocytes microglia
glial scar formation
A structural formation of reactive glia around an area of severe tissue damage. Caused by Myelin-associated inhibitors, astrocytes, oligodendrocytes, oligodendrocyte precursors and microglia
what causes glial scar formation
a response to tissue damage - myelin-associated inhibitors -astrocytes -oligodendrocytes - oligodendrocyte precursors - microglia
NG2 GLIA
polydendrocytes
NG2 GLIA cause
inhibition of axon regeneration by both expression of inhibitory:
- H2 proteoglycan
- As well as formation of synaptic contacts
outline simple steps of glial scar formation
1) Increase homeostatic and tropic functions of glial cells
2) Secretory activity e.g. cytokines and GF of glial cell
3) Proliferation of glial cells
4) Migration of glial cells
5) Glial scar formation and BBB repair
the BBB
BBB forms in blood vessels which surrounds most of the brain. Maintains tight junctions of endothelial cells ensuring the brain maintains its highly restricted environment
why is BBB important
prevents toxins and pathogens from entering the brain
the BBB is highly selective allowing
water, oxygen and LIPID SOLUBLE substances to pass through
how is glucose transported into the brain
actively transported
tight junction restrict
the space between endothelial cells
which glial cell supports the BB by surrounding blood vessels
astrocytic ends (think of picture
in a capillary there are…. between endothelial cells
fenestrations (gaps)
transcellular lipophilic pathway
lipid soluble agents diffuse through
glucose, amino acids and nucleosides are actively transported across the membrane
receptor mediated trancytosis
insulin transferrin
adsoprtive transcytosis
albumin and other plasma proteis (forms vesicle in outer membrane which cross the memrane to the other side
paracellular aqueous pathway
means water can still pass through tight junctions
astrocytes
surround blood vessels in the brain, helping to maintain tight junctions
- processes make cotnact with the BBB
- provide nutirents to the neurones by creating an interface to the blood
amoeboid astrocytes
acute disease
phagocytosing- mops up damaged cells
Astrocytes can take two forms
rod-like
amoeboid
rod-like astrocyte shape
Chronic disease
Lays down layer of rods
how do astrocytes support synapes
by recyling NT via retrograde signalling
microglia
survey for foreign obects, acting like macrophages (clear cellular debris and neurones using autophagy)
how do microglia help organise the brain
by destroying debris and unneeded neurones using autophagy
In TBI, receptors on microglia bind with
APoE (CTE)
microglia promote
inflammation
resting shape of microglia
ramified
ramified microglia
act as surveillance cells to maintain the homeostasis of the neuronal microenvironement
-directly remove dysfunction synaptic terminals to maintain the integrity of neuronal circuitry
rod-shaped/ bipolar microglia
have elongated cell bodies with their processes extended towards the two ends
- phagocytic in nature which involve the internalisatio of degenerating neurons after CNS injury
- invovled in neuronal circuit regorganisation via synaptic stripping
amoeboid microglia
- highly motile with few processes
- invole int ehe degradation of extracellula laminin
- acitvely pahgocytes cellular debrs and extrceullar protein aggregates such as B-amyloid and alpha-synuclein
- secrete neurotoxic factors which induce neruone cell death
which form of microglia cause neuronal cell death
amoeboid microglia by secreting pro-inflammatory cytokine
(IL-1B, TNFa, NO etc)
in a healthy CNS how are microglia displayed
as ramified microglia
in response to TBI, chronic neuroinflammation, LPS and bacteria-induced neuroinflamamtion etc ramified microglia change to
ameoboid microglia
LPS activation and chronic and sustained activation of microglia in later stages of neurodegeneration convert rod-shape microglia to
ameoboid microglia
scratched laminin-coated surgave, patients with paralytic dementia and chronic neuropathological disorders causes the conversion of ramified microglia to
rod-shaped
rod-like microglia are present into what sort of disease
chronic e.g. degenrative brain disorders
amoeboid microglia are present during…. disease
acute disease
when a micrgolia senses danger
- It becomes more compact, with the long arms contract inwards (ameboid).
- These microglia then start to multiply rapidly.
- They release cytokines to attract other immune cells, like T cells
- Also release chemicals which recruits neurones and astrocytes which helps the brain heal
three main types of microglia 9accoridng to loacation
cortex-ramified
corpus callosum
hippocampus
the gliovascuar unit
the BBB and glia (astroctyes and microglia) surrrounding it
the gliovascular unit explanation
The BBB and the astrocytes surrounding it- the receptors which go within that membrane to cause movement of ions such as TGF-B and other cytokines, glutamate transmitters.
Further surrounding this complex are microglia- ensure what goes in and out of the brain
within TBI patients
both immediate and delayed dysfunction of the BBB/gliovasuclar unit are observed
how is the BBB disrupted during TBI
disruption of tight junctions increases permebaility
- oxidative stress
- increased production of pro inflammatory mediators
- upregulation of cell adhesion molecules expression on the surface of the brain endotheliumàpromoting influx of inflammatory cell
