|Budget Amount *help
¥2,200,000 (Direct Cost : ¥2,200,000)
Fiscal Year 1998 : ¥400,000 (Direct Cost : ¥400,000)
Fiscal Year 1997 : ¥400,000 (Direct Cost : ¥400,000)
Fiscal Year 1996 : ¥1,400,000 (Direct Cost : ¥1,400,000)
Excessive release of excitatory amino acids such as glutamate and increased generation of free radicals such as reactive oxygen species (ROS) and nitric oxide (NO) are involved in mechanisms of cerebral damage during ischemia-reperfusion. Therefore extracellular glutamate release and NO generation were measured in vivo with microdialysis biosensor and microdialysis in rat forebrain isohemia - reperfusion model. Forebrain ischemia-reperfusion was performed by bilateral carotid artery occlusion (10 min) with controlled hemorrhagic hypotension (MAP = 30 mmHg). NO generation was determined by measuring NO end-products (nitrite and nitrate). The effect of hyperbaric oxygen (HBO) on generation of NO and ROS was also determined in rat model, where NO and ROS had been considered to increase (endotoxin injection, hemorrhagic shock and hyperbaric CNS oxygen toxicity).
1) Extracellular glutamate and NO release, and effects of NO synthase (NOS) inhibitor (L-NAME)
a) Extracellular glutamate levels in striatum, hippocampus and forebrain cortex increased biphasically upto about 6-fold during ischemia and returned to the baseline level within 30 mm after reperfusion. b) Nitrite increased during schemia and 40 min after reperfusion, however, nitrate changed in the opposite direction. c) NOS inhibition by L-NAME did not prevent ischemia-induced glutamate release, and increased glutamate level during reperfusion.
2) Effect of HBO on generation of NO and ROS
a) HBO did not suppress increased plasma levels of NO-endproducts (nitrite, nitrate) in endotoxin-treated rats. HBO significantly increased plasma nitrite and nitrate level in rats of hemorrhagic shock, which was induced by withdrawing blood until MAP = 40 mmHg for 30 mm and thereafter replaced by plasma expander. HBO, however, prolonged survival time compared to control rats. b) As the results of experiments using NO and ROS related agents, increased generation of NO and ROS take part in oxygen toxicity induced by HBO in ONS.