Effect of seizures induced by kainic acid on nitric oxide synthase of hippocampus

• Main Authors: Ai-Wei Lee, 李愛薇
• Other Authors: Yu-Show Fu
• Format: Others
• Language: zh-TW
• Published: 1999
• Online Access: http://ndltd.ncl.edu.tw/handle/25945497826776186683

碩士 === 國立陽明大學 === 解剖學研究所 === 87 === Nitric oxide (NO) is producted by NOS and may be an important diffusible messanger in the central nervous system (CNS). At least nNOS and eNOS responsible for the synthesis of NO have been reported to exist in the CNS, however, different localization of both NOSs occur in the hippocampus, it becomes most interesting to find their different expression in response to kainic acid (KA) stimulation. Acute effect of seizures induced by intraperitoneal injection of KA (10mg / kg) was conducted in adult rats, and after a survival interval of 1hr, 2hrs, 12hrs, 1day, 7days, and 30days. 1hr after KA administration the rats expose masticatory movements, myoclonic twitches, and severe limbic motor seizures. The ambulatory time and distance travel increased 1hr after KA injection, and maintained the activity up to 1 month. The NOS activity assay showed that the activity of the hippocampus membranes decreased from (3505±131.8) CPM/mg protein at control group to (2010±121.4) CPM/mg protein at 15min after KA injection. At 12hr the activity increased slightly to (2750±59.6) CPM/mg protein and then decrease to (2425±251.5) at 1D and persisted until 7 day after KA injection. Western blot analyses reveal that the quantity of membrane-bound eNOS and nNOS were not significantly different flowing KA application. The concentration of soluble nNOS and eNOS were 30 % lower than control group by 1hr, and maintained the concentration thereafter. Cresyl violet staining, eNOS and nNOS immunocytochemistry examination confirmed that the number of hippocampal neurons was decreased at 1h or 2hr after KA injection and persisted until 1 month. Moreover, system injections of the NOS inhibitors N-nitro-L-Arginine methyl ester (L-NAME) and 7-nitroindazole (7-NI) prior to KA , both at a dose of 10mg/kg , reduced cell death in all subregions . In conclusion, hippocampal NOS activity was decreased after KA injection, resulting from the damage of NOS neurons. Moreover, pretreatment with NOS inhibitor L-NAME and 7-NI protect rat hippocampus against KA-induced seizures.