title: Protection against hypoxic/ischaemic brain damage with excitatory amino acid antagonists.
abstract: Selective neuronal loss in the hippocampus following transient forebrain ischaemia appears to be excitotoxic in origin. The early cytological changes in the rat hippocampus (1-2 hours after 10 or 30 minutes of ischaemia) have the ultrastructural appearances of an excitotoxic lesion. Focal injection of an excitatory amino acid antagonist acting competitively on the N-methyl-D-aspartate (NMDA) receptor, 2-amino-7-phosphonoheptanoic acid (2-APH) in one hippocampus protects against the early cytopathology, and, when repeated 4 and 10 hours after the ischaemia, partially protects against selective nerve cell loss. Systemic administration of 2-APH or of a non-competitive antagonist at the NMDA receptor, ketamine, also protects against neuronal loss. Blockade of excitatory transmission at the NMDA receptor may provide a therapeutic approach to the acute treatment of cerebral ischaemia.
mesh_terms: D000596:Amino Acids / Q000037:antagonists & inhibitors*; D000818:Animals; D001925:Brain Damage, Chronic / Q000209:etiology / Q000517:prevention & control*; D002545:Brain Ischemia / Q000503:physiopathology*; D006624:Hippocampus / Q000503:physiopathology*; D006801:Humans; D002534:Hypoxia, Brain / Q000503:physiopathology*; D018377:Neurotransmitter Agents / Q000037:antagonists & inhibitors*
chemical_list: D000596:Amino Acids; D018377:Neurotransmitter Agents