| Co-Investigator(Kenkyū-buntansha) |
WATANABE Ippei Niigata University Hospital Assistant, 医学部・附属病院, 助手 (00251819)
TANAKA Eiichiro Kurume University School of Medicine Lecturer, 医学部, 講師 (80188284)
HASHIBA Masao Niigata University Hospital Lecturer, 医学部・附属病院, 講師 (30108047)
SATO Kazunori Niigata University Hospital Lecturer, 医学部・附属病院, 講師 (70126415)
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| Research Abstract |
1) Acidosis is thought to be one of the causes of ischemic neuronal damage. However, in rat hippocampal slices under mildly acidotic conditions (pH 6.7-6.8), a characteristic rapid [Ca^<2+>]_i increase and rapid depolarization induced by oxygen-glucose deprivation were slowed and retarded, and recovery of field potential following 10 min of oxygen-glucose deprivation was improved. The results suggest that mild acidosis protects hippocampal neurons against ischemic damage.
2) Depolarizing agents, including high K^+, veratridine and NMDA,elicited a decrease in pH_i and an elevation of [Ca^<2+>]_i in the CA1 pyramidal cell layr. Although the [Ca^<2+>]_i increase was almost completely suppressed in Ca^<2+> -free media, a major part of each pH_i acid shift remained unchanged. Glucouse-deprivation reduced pH_i acid shifts induced by both high K^+ and NMDA by two-third. Lactate contents significantly increased in slices exposed to the depolarizing agents. The results suggest that pH_i acid shifts produced by the depolarizing agents are mainly due to lactate accumulation by accelerated glycolysis. A Ca^<2+> -dependent process may also contribute in part to pH_i acid shifts. Since an increase in [H^+] decreases neuronal excitability, glycolytic acid production promoted by membrane depolarization may contribute to prevent excessive neuronal excitation. 3) Neuronal excitability was optically recorded in gerbil hippocampal slices, which was prepared 18-20 hr after transient forebrain ischemia for 4 min, using a potential sensitive dye. When Schaffer collaterals were electrically stimulated, neuronal excitation was spreaded within the same stratum and orthodromic spreading to strata pyramidale and oriens was inhibited. Thus, neuronal dysfunction might already occur 18-20 hr after the transient ischemia, although degeneration of pyramidal neurons was not found.
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