Excitotoxicity

Question 1

what is excitotoxicity?

Answer 1

a balance between the activity of inhibitory and excitatory neurons in the brain is essential for proper function

Question 2

the disruption to excitatoxicity can be due to?

Answer 2

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)

Question 3

what are neurotransmitters responsible for?

Answer 3

for signals between and from neurons

Question 4

typically, what happens to NTs?

Answer 4

they are stored, released and then recaptured

Question 5

inhib or excit? glutamate?

Answer 5

it is excitatory

Question 6

inhib or excit? GABA?

Answer 6

it is inhibitory

Question 7

Glutamate?

Answer 7

most abundant neurotransmitter
act on both ionotropic and metabotropic receptors

Question 8

ionotropic receptor?

Answer 8

fast, NMDA receptors (cations)
AMPA receptors (Na+, K+, structure dependent Ca2+)
Third type: kainate

Question 9

metabotropic receptor?

Answer 9

they are also known as GPCRs - they are slow

Question 10

what do glutamate transporters do?

Answer 10

they help remove excess glutamate

Question 11

GABA stands for?

Answer 11

gamma-amino butyric acid

Question 12

what is GABA?

Answer 12

major inhibitory neurotrasnmitter

Question 13

two type of GABA receptors?

Answer 13

ionotropic receptor
metabotropic receptor

Question 14

describe the GABA ionotropic receptor?

Answer 14

it is fast and linked to Cl- channels

Question 15

describe the GABA metabotropic receptor?

Answer 15

it is slow and mediated by K+ channels

Question 16

Imbalances between excitation and inhibition in the brain may lead to?

Answer 16

to excessive excitation

Question 17

What can desynchronisation of neuronal firing lead to?

Answer 17

to seizures

Question 18

what is a seizure?

Answer 18

clinical manifestation of an abnormal and excessive excitation of a population of neuron (all together)

Question 19

what is epilepsy?

Answer 19

a situation in which there is recurrent episodes of seizures which is unprovoked by any systemic or acute pathology

Question 20

what is the mechanism of a seizure?

Answer 20

Excitation (too much):
ionic - inward Na+, Ca2+ currents
- neurotransmitter - glutamate, aspatate
Inhibition (too little)
ionic - inward Cl-, outward K+ currents (reduced)
neurotransmitter - GABA

Question 21

tonic-clonic action?

Answer 21

common feature in a seizure
muscle contracts then relaxes in regular timings
clonic - rhythmic contraction
tonic - sustained contraction - extension, arching back, stretching

Question 22

simple seizure?

Answer 22

patient is conscious

Question 23

complex seizure?

Answer 23

patient is unconscious

Question 24

how does excitotoxicity result in seizures?

Answer 24

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

Question 25

how can we reduce swelling of the spinal cord?

Answer 25

with NSAIDs or steroids and TIME (very important, just wait)

Question 26

swelling from inflammation of the spinal cord will...

Answer 26

it will reduce function

Question 27

what does ivermectin do?

Answer 27

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

Question 28

what do local anaesthetics do?

Answer 28

inhibit Na+ influx through voltage-gate Na+ channels in neuronal cell membranes influx of sodium is interrupted - propagation of action potential inhibited