The chronic administration of docosahexaenoic acid reduces the spatial cognitive deficit following transient forebrain ischemia in rats

被引:80
作者
Okada, M
Amamoto, T
Tomonaga, M
Kawachi, A
Yazawa, K
Mine, K
Fujiwara, M
机构
[1] FUKUOKA UNIV,FAC PHARMACEUT SCI,DEPT PHYSIOL & PHARMACOL,FUKUOKA 81401,JAPAN
[2] FUKUOKA UNIV,SCH MED,DEPT NEUROSURG,FUKUOKA 81401,JAPAN
[3] SAGAMI CHEM RES CTR,KANAGAWA 229,JAPAN
[4] KYUSHU UNIV,FAC MED,DEPT PSYCHOSOMAT MED,FUKUOKA 812,JAPAN
关键词
docosahexaenoic acid; arachidonic acid; cerebral ischemia; memory; hypoxia; NADH;
D O I
10.1016/0306-4522(95)00427-0
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The purpose of this study was to investigate whether chronic administration of docosahexaenoic acid is able to reduce spatial cognitive deficit following transient ischemia in rats. In addition, we investigated whether the chronic treatment of docosahexaenoic acid is able to protect the hippocampal neuronal damage induced by either hypoxia in vitro or cerebral ischemia in vivo. A chronic administration of 200 mg/kg/day docosahexaenoic acid over 21 days did not affect the content of docosahexaenoic acid in the hippocampus, but did tend to increase it in the frontal cortex. On the other hand, this chronic administration decreased the content of arachidonic acid significantly both in the hippocampus and the frontal cortex. Under hypoxic conditions, the onset of the increase in the NADH fluorescence in the hippocampal slice was made significantly slower relative to the control by the chronic administration of docosahexaenoic acid. Rats were subjected to 10 min of transient forebrain ischemia by the method of four-vessel occlusion and were tested in a radial eight-arm maze task after cerebral reperfusion. Docosahexaenoic acid was administered either once 1 h before occlusion or daily for 21 days before occlusion. The single treatment of docosahexaenoic acid (1, 10, 100 or 200 mg/kg) did not significantly affect any aspect of the spatial learning deficit following occlusion. On the other hand, chronic treatment with docosahexaenoic acid (10, 100 or 200 mg/kg/day) significantly improved the spatial learning deficit following occlusion. A comparison of the neuronal densities in the hippocampal CA1 region of the chronically docosahexaenoic acid-treated (200 mg/kg/day) rats with those of the ischemic control revealed a significant neuronal preservation. From these results, it appears that chronic administration of docosahexaenoic acid may be valuable in ameliorating the spatial cognitive deficit induced by transient forebrain ischemia. In addition, docosahexaenoic acid might contribute to the protection of hippocampal neuronal damage caused by either hypoxia or ischemia.
引用
收藏
页码:17 / 25
页数:9
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