Taming glutamate excitotoxicity: strategic pathway modulation for neuroprotection

Abstract

Much work has been carried out in recent years showing that elevated glutamate levels in the extracellular environment of the central nervous system play a pivotal role in neurodegeneration in acute CNS injuries. With the elucidation of the mechanism governing glutamate excitotoxicity, researchers are devising therapeutic strategies to target different parts of the pathway which begins with glutamate accumulation and ultimately results in neuronal cell death. In this article, we review some of the major classes of agents that are currently being investigated and highlight some of the key studies for each. Glutamate scavenging is a relatively new approach that directly decreases glutamate levels in the brain, thus preventing excitotoxicity. Nitric oxide inhibitors and free radical scavengers are more well-studied strategies that continue to yield promising results.