The role of free radicals in cerebral hypoxia and ischemia

This review focuses on the effects that ischemia and hypoxia have on the cerebral cortex and the cerebellum during different periods of life. The acute interruption or reduction of cerebral blood flow, that can be induced by several factors and clinical pathologies, reduces available oxygen to the nervous system and this causes either focal or global brain damage, with characteristic biochemical and molecular alterations that can result in permanent or transitory neurological sequelae or even death. Under these circumstances, an increase in the activity of different isoforms of nitric oxide synthase occurs and nitric oxide is produced. This excess of nitric oxide reacts with cellular proteins yielding nitrotyrosine, thus contributing to cerebral damage. This phenomenon has been studied at different stages of perinatal and postnatal development, including aging animals. Both the duration and the intensity of the ischemic injury were evaluated. In all cases there is overproduction of nitric oxide in ischemia, which may represent an effort to reestablish normal blood flow. Unfortunately, in many cases this response becomes excessive and it triggers a cascade of free-radical reactions, leading to modifications of cerebral plasticity and overt injury.