Excitotoxicity Flashcards
what is excitotoxicity?
a balance between the activity of inhibitory and excitatory neurons in the brain is essential for proper function
the disruption to excitatoxicity can be due to?
too little signalling
(too much inhibition/too little excitation –> potential consequence: coma/PVS)
too much signalling
(too much excitation/too little inhibition
–> potential consequence: seizures, Alzheimer’s)
what are neurotransmitters responsible for?
for signals between and from neurons
typically, what happens to NTs?
they are stored, released and then recaptured
inhib or excit? glutamate?
it is excitatory
inhib or excit? GABA?
it is inhibitory
Glutamate?
most abundant neurotransmitter
act on both ionotropic and metabotropic receptors
ionotropic receptor?
fast, NMDA receptors (cations)
AMPA receptors (Na+, K+, structure dependent Ca2+)
Third type: kainate
metabotropic receptor?
they are also known as GPCRs - they are slow
what do glutamate transporters do?
they help remove excess glutamate
GABA stands for?
gamma-amino butyric acid
what is GABA?
major inhibitory neurotrasnmitter
two type of GABA receptors?
ionotropic receptor
metabotropic receptor
describe the GABA ionotropic receptor?
it is fast and linked to Cl- channels
describe the GABA metabotropic receptor?
it is slow and mediated by K+ channels
Imbalances between excitation and inhibition in the brain may lead to?
to excessive excitation
What can desynchronisation of neuronal firing lead to?
to seizures
what is a seizure?
clinical manifestation of an abnormal and excessive excitation of a population of neuron (all together)
what is epilepsy?
a situation in which there is recurrent episodes of seizures which is unprovoked by any systemic or acute pathology
what is the mechanism of a seizure?
Excitation (too much):
ionic - inward Na+, Ca2+ currents
- neurotransmitter - glutamate, aspatate
Inhibition (too little)
ionic - inward Cl-, outward K+ currents (reduced)
neurotransmitter - GABA
tonic-clonic action?
common feature in a seizure
muscle contracts then relaxes in regular timings
clonic - rhythmic contraction
tonic - sustained contraction - extension, arching back, stretching
simple seizure?
patient is conscious
complex seizure?
patient is unconscious
how does excitotoxicity result in seizures?
there is prolonged opening of glutamate receptors and continuous depolarisation in seizure
causes cell to swell and rupture (Na+ and H2O entry)
continued excitation causes toxic build up of intracellular calcium
alter the intracellular environment leading to disruption in intracellular organelle function
There is over activation of Ca2+ - activated protease activity and the subsequent activation of program cell death
how can we reduce swelling of the spinal cord?
with NSAIDs or steroids and TIME (very important, just wait)
swelling from inflammation of the spinal cord will…
it will reduce function
what does ivermectin do?
it opens invertebrate specific glutamate-chloride channels in post-synaptic membrane of nematode worms and an agonist of GABA, leading to hyperpolarisation, flaccid paralysis and death
what do local anaesthetics do?
inhibit Na+ influx through voltage-gate Na+ channels in neuronal cell membranes
influx of sodium is interrupted - propagation of action potential inhibited
