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The role of glutamate in neuronal ischemic injury: the role of spark in fire

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Abstract

Although being a physiologically important excitatory neurotransmitter, glutamate plays a pivotal role in various neurological disorders including ischemic neurological diseases. Its level is increased during cerebral ischemia with excessive neurological stimulation causing the glutamate-induced neuronal toxicity, excitotoxicity, and this is considered the triggering spark in the ischemic neuronal damage. The glutamatergic stimulation will lead to rise in the intracellular sodium and calcium, and the elevated intracellular calcium will lead to mitochondrial dysfunction, activation of proteases, accumulation of reactive oxygen species and release of nitric oxide. Interruption of the cascades of glutamate-induced cell death during ischemia may provide a way to prevent, or at least reduce, the ischemic damage. Various therapeutic options are suggested interrupting the glutamatergic pathways, e.g., inhibiting the glutamate synthesis or release, increasing its clearance, blocking of its receptors or preventing the rise in intracellular calcium. Development of these strategies may provide future treatment options in the management of ischemic stroke.

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  1. Department of Pharmacology, Faculty of Medicine, University of Assiut, Assiut, 71526, Egypt

    Botros B. Kostandy

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Kostandy, B.B. The role of glutamate in neuronal ischemic injury: the role of spark in fire. Neurol Sci 33, 223–237 (2012). https://doi.org/10.1007/s10072-011-0828-5

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