Protection against hypoxic/ischaemic brain damage with excitatory amino acid antagonists.
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.
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*
D000596:Amino Acids; D018377:Neurotransmitter Agents