ISCHEMIC-INJURY AND EXTRACELLULAR AMINO-ACID ACCUMULATION IN HIPPOCAMPAL AREA CA1 ARE NOT DEPENDENT UPON AN INTACT SEPTOHIPPOCAMPAL PATHWAY

The septo-hippocampal pathway contains a major gamma-aminobutyric acid (GABA) projection to dendritic fields within the hippocampus. To dete rmine the importance of the septo-hippocampal pathway in ischemia-indu ced accumulation of GABA and subsequent cell death in area CA1 of hipp ocampus, septo-hippocampal deafferentation of adult gerbils was perfor med. Electrolytic lesions were produced in the medial or medial plus l ateral septal regions in gerbils 7 days prior to being subjected to 5 min forebrain ischemia. The extent of deafferentation of the dorsal hi ppocampus was determined histochemically by acetylcholinesterase stain ing. Both the medial and medial plus lateral septal lesions produced n early complete loss of acetylcholinesterase staining in the dorsal hip pocampus indicating relatively complete deafferentation. During and fo llowing ischemia, in vivo microdialysis was used to measure extracellu lar GABA accumulation, which reached concentrations up to 1060 +/- 143 % of basal. Septo-hippocampal deafferentation in both groups of lesion ed animals failed to prevent the accumulation of GABA (and glutamate) induced by ischemia, indicating that ischemia-induced GABA accumulatio n in area CA1 arises principally from intrinsic GABAergic interneurons . Ischemic animals with medial septal lesions did not demonstrate neur oprotection or increased damage in the stratum pyramidale 7 days after reperfusion. Since the septo-hippocampal pathway provides the source of GABAergic disinhibition within the hippocampus, neither disinhibiti on nor the septo-hippocampal input appear to play an important role in the development of ischemia-induced neuronal death in the hippocampus . (C) 1998 Elsevier Science B.V.