Protective effect of protease inhibitors (urinastatin, gabexate mesilate and nafamostat mesilate) on brain edema and energy metabolism following cerebral ischemia or hypoxia

Abstract

The effects of three different kinds of protease inhibitors (PI) were studied in cerebral hypoxia or ischemia using spontaneously hypertensive rats. The agents tested were urinastatin (US), gabexate mesilate (GM) and nafamostat mesilate (NM). We investigated the agents under cerebral hypoxia induced by placing rats in a chamber containing 96% nitrogen and 4% oxygen for 30 min. Cerebral ischemia was produced by bilateral common carotid artery occlusion for 2 hr followed by 30 min reperfusion. In the experiment on hypoxia, the brain water content did not change after the hypoxia. The brain ATP levels in the PI-administered groups were higher and the lactate levels in the PI-treated groups were lower than those in the controls. In the experiment on ischemia, the percentage brain water contents was significantly decreased in the PI-administered groups as compared to the control group. The brain ATP levels in the PI-treated groups were higher than those in the control group. The values of the lactate/pyruvate ratio were significantly decreased compared to the control group. These findings suggest that PI agents might be useful in the treatment of cerebral hypoxia or ischemia.