Ischemic injury and extracellular amino acid accumulation in hippocampal area CA1 are not dependent upon an intact septo-hippocampal pathway.
The septo-hippocampal pathway contains a major gamma-aminobutyric acid (GABA) projection to dendritic fields within the hippocampus. To determine the importance of the septo-hippocampal pathway in ischemia-induced accumulation of GABA and subsequent cell death in area CA1 of hippocampus, septo-hippocampal deafferentation of adult gerbils was performed. Electrolytic lesions were produced in the medial or medial plus lateral septal regions in gerbils 7 days prior to being subjected to 5 min forebrain ischemia. The extent of deafferentation of the dorsal hippocampus was determined histochemically by acetylcholinesterase staining. Both the medial and medial plus lateral septal lesions produced nearly complete loss of acetylcholinesterase staining in the dorsal hippocampus indicating relatively complete deafferentation. During and following ischemia, in vivo microdialysis was used to measure extracellular GABA accumulation, which reached concentrations up to 1060 +/- 143% of basal. Septo-hippocampal deafferentation in both groups of lesioned animals failed to prevent the accumulation of GABA (and glutamate) induced by ischemia, indicating that ischemia-induced GABA accumulation in area CA1 arises principally from intrinsic GABAergic interneurons. Ischemic animals with medial septal lesions did not demonstrate neuroprotection 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 disinhibition nor the septo-hippocampal input appear to play an important role in the development of ischemia-induced neuronal death in the hippocampus.
Gabriel
E M
EM
Department of Surgery (Division of Neurosurgery), Duke University Medical Center, Durham, NC 27710, USA.
Inglefield
J R
JR
Chadwick
L E
LE
Schwartz-Bloom
R D
RD
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D004572:Electrolysis; D005110:Extracellular Space; D005849:Gerbillinae; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism* / Q000502:physiology / Q000503:physiopathology; D002546:Ischemic Attack, Transient / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D017551:Microdialysis; D009434:Neural Pathways / Q000502:physiology / Q000503:physiopathology*; D016548:Prosencephalon; D017966:Pyramidal Cells / Q000378:metabolism / Q000502:physiology; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D000110:Acetylcholinesterase