RT Journal Article ID 179746032e1b332e A1 Strijbos, Paul J. L. M. T1 Nitric Oxide in Cerebral Ischemic Neurodegeneration and Excitotoxicity JF Critical Reviews™ in Neurobiology JO CRN YR 1998 FD 1998-09-30 VO 12 IS 3 SP 223 OP 243 K1 free radicals K1 stroke K1 central nervous system K1 neuronal death K1 glutamate AB The observation that the free radical nitric oxide (NO) acts as a cell signaling molecule in key physiological processes such as regulation of blood pressure and immunological host-defense responses is probably one of the most important and exciting findings made in biology in the last decade. Likewise, in the brain NO has been implicated in a number of fundamental processes, including memory formation, sexual behavior and the control of cerebral blood flow. This has radically altered the accepted dogma of brain physiology and has placed NO at the center stage of neuroscience research. Evidence suggests that some of the actions of NO in the brain may be intimately linked to those of the classic excitatory neurotransmitter glutamate. The historical view that aberrations in glutamate signal transduction may underlie central neurodegeneration following, for example, cerebral ischemia, has implicated NO, by default, as a potential mediator of neuronal death. Indeed, with the advent of potent and specific compounds that interact with NO synthesizing (NOS) enzymes and with the NO signaling cascade, there is now ample evidence to suggest that NO can mediate neurodegeneration, although its involvement is paradoxical. Its cerebrovascular effects may act to limit ischemic damage by preserving tissue perfusion and preventing platelet aggregation, while NO produced in the parenchyma, either directly following the ischemic insult or at a later stage as part of a neuroinflammatory response, may be deleterious to the outcome of ischemia. Nonetheless, significant efforts are made into the potential therapeutic use of chemical NO donors and specific NOS inhibitors in the treatment of cerebral ischemia and other central neurodegenerative disorders. Here, the latest concepts and developments in our understanding of the role of NO in cerebral ischemic neurodegeneration are discussed. PB Begell House LK https://www.dl.begellhouse.com/journals/7b004699754c9fe6,7ddb5c405a994f83,179746032e1b332e.html