Role of Platelets in Glutamate Mediated Excitotoxicity: An Overview

Abstract

Glutamate, the main excitatory neurotransmitter in central nervous system (CNS), binds primarily to two types of receptors on the post-synaptic membrane of neuronal cells, namely metabotropic receptors and ionotropic receptors. Metabotropic receptors are G-protein coupled receptors while ionotropic receptors are non-selective ligand-gated ion channels, which allow movement of cations like Na+, K+ and Ca2+. The three most studied ionic receptors are N-methyl-D-aspartate receptor (NMDAR), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), and Kainate receptor. Glutamate synapse plays a pivotal role in many neurodegenerative disorders like Huntington disease, trauma, epilepsy, Alzheimer and Amyotrophic lateral sclerosis, and cerebral ischemia. Understanding the mechanism of these glutamate ligand-gated ion channels (LGIC) can assist in the development of therapy against ischemic stroke, a leading cause of death and disability worldwide. This review focuses on how aggregated platelet microthrombi cross blood-brain barrier, reach neural parenchyma and release glutamate. Accumulated glutamate hyperstimulates glutamate LGIC, thus leading to neurotoxicity and apoptosis of neuronal cells.