Homeostasis in the CNS 1 & 2 Flashcards
what is in a neural microenvirnomennt
glia
neurons
capillaries
extracellular space
ECM
BECF - interstitial fluid
changes in BECF composition
can both influence or be influenced by other neurons
increased activity in neuron leads to change in BECF which increases neuronal activity
if the cycle becomes uncontrolled = neuronal dysfunction and death
so BECF composition must be tightly regulated
how do we regulate neuronal microenvironment, including BECF?
blood brain barrier
CSF in ventricular system
neurons
glial cells and astrocytes
how could BECF composition be affected by increased neuronal activity?
increased K, changes is Ca, O2, CO2 and glucose concentration and different concs of neurotransmitters
how could a change in BECF change neuronal activity?
increase in K in BECF changes resting potential bringing cell closer to threshold for firing action potential
inc neurot release could lead to unspecific neural activity
blood brain barrier
revealed by IV injection of dyes
dye passes through leaky capillaries
stain soft tissues and all organs (inc spinal cord) apart from brain
so brain must have something to stop things leaking into and out of it
function = protect neurons from fluctuations in concentration of substances in blood
e.g. amino acid conc increases after a meal - dont want in brain as could act as unspecific neurot
same for increases in K and H after exercise
maintaining blood brain barrier
tight junctions between endothelial cells
thick basment membrane - additional layer that molecules have to get through
astrocytic endfeet
brain capillaries dont have intracellular clefts or fenestra
all form barriers to stop molecules getting into BECF
how do important molecules get through
facilitated transport
exchangers
co-transporters
means that treating dieseases in brain is difficult as most things cant get through
small, uncharged and/or lipid soluble molecules can pass through more easly such as CO2, nicotine, heroine, caffine
leaky regions
choroid plexuses - ventricular system
circumventricular organs
in these ares ependymal cells beneath have tight junctions to protect rest of brain
why have leaky regions?
in brain there are osmoreceptors and temp control centres that need to send hormones from pituitary into circulation
CSF in ventricular system
ventircular system = fluid filled cavity for physical protection, maintaining ion levels and removing waste
secreted by choroid plexuses - constant production, some in lateral, 3rd and 4th ventricle
circulates around ventricles and central canal, moves around brain and absorbed by subarachnoid space to return to venous vlood system by superior sagittal sinus
foramens allows CSF out of central canal and back up to sinus
sinus
something that drains into venous system
secretion of CSF
500mls/day
3 mechanisms:
ultrafiltration of plasma into ECF across normal ‘leaky’ capillaries = free movement
selective absorption of substances into CSF across choroidal epithelial cells = regulated movement
free movement of substances from CSF to BECF across ependymal cells = free movement
structure of choroid plexus
outer epithelium separates brain tissue from ventricular system, made of leaky ependymal cells so CSF can move freely into brain
choroidal epithelium contains pockets of fluid with tight junctions to separate it from CSF
what is in CSF?
K
amino acids
proteins
much higher plasma than CSF
outwards bumps on cerebral cortex
giri
inward bumps on cerebral cortex
sulci
the meninges
membranes around brain and spinal cord
leptomeninges:
pia mater
arachnoid mater
dura mater
pia mater
innermost
thin
permeable
allows diffusion
arachnoid mater
separated by CSF in subarachnoid space, has tight junctions
dura mater
can split into 2 layers, one clings to bumps on cerebral cortex, other is more circular
absorption of CSF
evaginations of arachnoid membrane:
arachnoid granulations
arachnoid villi
both do same thing and project through duramater into sinus space
single layer of cells joined by tight junctions
an increase in pressure sue to constant production of CSF leads to the membrane pinching CSF and transporting back into circulatory system
so inc absorption with inc intercranial pressure
exchange between CSF and BECF?
exchange occurs from ventricles across ependymal cells and from subarachnoid space across pia mater - doesnt have tight junctions
CSF —-> BECF
macronutrients e.g. glucose
micronutrients e.g. vitamins
ions e.g. HCO3
BECF —-> CSF
metabolic waste products e.g. CO2
neurotransmitters
what if CSF cannot circulate properly?
leads to hydrocephalus
due to blockage in ventricular system, usally in cerebral aqueduct as its so thin
constant production of CSF leads to major swelling of brain
- dilation of ventricular system
can also be caused by interrupted CSF absorption but a blockage is more likely
- inc intercranial pressure
- loss of cells in brain
- loss of brainstem reflexes - swelling pushes on brainstem = cant regulate heart rate etc
tripartite synapse
neurons, glial cells and astrocytes
neurons and astrocytes work together to clear neurot from BECF an terminate neurotransmission
e.g. glutamate needs to be removed from cleft or it will continuously signal
EAAT3 - recycles glutamate into pre syn terminal
EAAT1/2 - moves neurot into astrocytes - breaks dwon into glutamine to recycle in pre syn terminal
neurons and astrocytes removing K from extracellular space
goes back into cell to maintain low extracell K
inc extracell K affects astrocyte function
inc K uptake means astrocyte moves more K into cell which drives ic in glucose metabolism = more ATP so ATPase pump works faster
why do neurons ahve -65 resting potential but glia have -85 when their eqm potenital for K is around the same?
neuronal membranes are more permeable to Na than astrocyte membranes, astros have higher K sensitivity = more selective = more extra cell K with influence Vm
astrocytic syncytium
allows spatial buffering
gap junctions create syncytium = lots of astrocytes joined to each other with electrical synapses that couple them together
redistributes K to areas of decreased activity
can transport sugars, aa, cAMP and Ca
neurovascular coupling
inc neuron firing rate —- astrocyte Ca inc —- release of vasoactive substances from astrocyte —- blood vessel diameter increase
joining activity of neurons to vasculature
functional imaging techniques
MRI allows 3D structural images of brain
how to measure activity:
- active neruons need more glucose and O2
- more blood directed to those areas
- 2 techniques detect changes in blood flow
positron emission tomography (PET)
exploits glucose use in brain
fMRI
exploits O2 use in brain
uses electromagnetic wave to disrupt H atom state
Blood Oxygen Level Dependant - BOLD
oxyhemoglobin and deoxy distort the magnetic resonance properties if H atoms differently