Under physiological conditions, neurotransmitters shape neuronal networks and control several cellular and synaptic functions. In the mammalian central nervous system (CNS), excitatory and inhibitory neurotransmission are mediated in large part by glutamate and gamma-aminobutyric acid (GABA), which are excitatory and inhibitory neurotransmitters, respectively. Glutamate and GABA also play crucial roles in neurological disorders such as cerebral ischemia. Glutamate in particular causes excitotoxicity, known as one of the hallmark mechanisms in the pathophysiology of cerebral ischemic injury for more than thirty years. Excitotoxicity occurs due to excessive glutamate release leading to overactivation of postsynaptic glutamate receptors, which evokes a downstream cascade that eventually leads to neuronal dysfunction and degeneration. Also, a reduction in GABA receptor response after ischemia impedes these inhibitory effectors from attenuating excitotoxicity and thereby further enabling the excitotoxic insult. This review focuses on the mechanisms by which glutamate and GABA mediate excitotoxicity and ischemic injury.
This article is part of the Special Issue entitled ‘Cerebral Ischemia’.