Nitrogen and oxygen radicals in ischemic and hypoxic injury of the brain

The purpose of this work was to examine the role played by a deficit in nitric oxide (NO) and overproduction of superoxide ($O-2$) and peroxynitrite (ONOO−) in contributing to the large cerebral infarcts seen in hypertensive and/or old animals. The role of NO-mediated mechanism in hypobaric hypoxia has been also studied. Additionally, the positive effect of the hypoxic adaptation on cerebral ischemia and reperfusion (I/R) has been demonstrated.; Cerebral infarction was produced in rats by occlusion of the middle cerebral artery followed by reperfusion. Studies were performed in animals of different age, genotype (spontaneously hypertensive stroke-prone), animals subjected to NO synthase blockade, and animals subjected to hypobaric hypoxia followed by adaptation process (30 days at 5,000 m above sea level).; NO and $O-2$ released in the brain were monitored using a set of specially designed microsensors with a 1 nM detection limit for both NO and $O-2$.; The direct relationships between: ONOO− concentration and infarct size, age and infarct size, and between altitude and both NO and $O-2$ concentrations released from the brain, have been established. Moreover, new evidence has been presented that neuroprotective properties of adaptation to hypoxia are solely due to an increase in bioactive NO.