Open Access

REVIEW

The Role of Glutamate Receptors in Ischemic Stroke

Long Qi¹, Chaoran Wu¹, Hao Sun^1,2,*, Hong Liao^1,*

1 New Drug Screening and Pharmacodynamics Evaluation Center, China Pharmaceutical University, Nanjing, 210009, China
2 Chongqing Innovation Institute of China Pharmaceutical University, Chongqing, 401135, China

* Corresponding Authors: Hao Sun. Email: ; Hong Liao. Email:

(This article belongs to the Special Issue: Cell Death and Inflammation in Signaling and Diseases)

BIOCELL 2025, 49(2), 167-180. https://doi.org/10.32604/biocell.2025.059159

Received 29 September 2024; Accepted 16 December 2024; Issue published 28 February 2025

Abstract

Glutamate is an essential excitatory neurotransmitter in the brain, playing a vital role in regulating synaptic activity and maintaining the homeostasis of the cerebral environment but also serves as a central hub for neuronal injury and inflammatory responses. In various pathological conditions, such as ischemic stroke, glutamate is released and accumulates excessively in the brain, leading to heightened stimulation of neurons and excitotoxicity. This phenomenon positions glutamate as a primary inducing factor for neuronal damage following cerebral ischemia. Glutamate exerts its effects primarily through two types of receptors: ionotropic and metabotropic glutamate receptors, both of which are extensively distributed throughout the hippocampus and cortical regions of the brain. Ionotropic receptors mediate rapid excitatory neurotransmission upon activation by glutamate; these are mainly categorized into N-methyl-D-aspartate receptors (NMDARs), α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors (AMPARs), and kainate receptors (KARs). Conversely, metabotropic receptors function as G-protein-coupled receptors (GPCR) facilitating glutamatergic cellular effects via intracellular second messenger. With the comprehensive investigation of glutamate receptors and their structural characteristics, our understanding of the nerve damage and protective mechanisms associated with glutamate receptors in ischemic stroke is progressively advancing. Consequently, exploring the role of glutamate receptors and their downstream signaling pathways in cerebral ischemia can provide a robust theoretical foundation for targeted therapies aimed at treating cerebral ischemia, stroke, and related disorders. This article reviews the function of glutamate receptors and their mediated downstream signal transduction pathways in the context of ischemic brain injury.

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