User:Akshita Roy/sandbox

PATHOPHYSIOLOGY
During the neonatal developmental stages, numerous pathophysiological mechanisms, lead to excessive excitation and reduced inhibition, which lowers their seizure threshold when compared with that of adults. This has been proved in animal(rodent) models wherein the adult and infant models are administered with the chemoconvulsant agent and their threshold seizure potential is compared. This lowered seizure threshold potential makes the neonatal brain susceptible to acute symptomatic seizures.


 * SEIZURE RISK DUE TO DECREASED INHIBITION: Gamma-butyric acid (GABA) is the main inhibitory neurotransmitter in adult humans. Upon binding with its receptor i.e GABAa, it causes hyperpolarisation of the neuronal membrane by causing the net influx of chloride ions. This hyperpolarisation leads to inhibition of further action potentials. However, in neonates, there is a relatively high expression of NKCC1(sodium-potassium-chloride cotransporter 1) than KCC2(potassium-chloride cotransporter 2). NKCC1 causes net efflux of chloride ions while KCC2 is responsible for causing a net influx of chloride ions . Increased expression of NKCC1 leads to depolarisation of the neuronal membrane. This depolarisation removes voltage-dependent Mg from N-methyl-D-aspartate(NMDA) receptors and triggers calcium influx. The binding of calcium to the receptors causes the generation of secondary messengers that increases the risks of seizures and increase the excitability of the brain.
 * SEIZURE RISK DUE TO INCREASED ACTIVATION: Glutamate is the primary excitatory neurotransmitter and the expression of its receptor is developmentally regulated . It binds to NMDA receptors, kainite receptors, and AMPA receptors. In course of the developmental stages, in several parts of the brain, a subunit of NMDA receptor-GluN2B is highly expressed which increases calcium influx. This mechanism increases the duration of postsynaptic currents in the immature brain in comparison to adult brains.