Mechanisms of brain injury after global cerebral ischemia.
Cerebral ischemia results in a rapid depletion of energy stores that triggers a complex cascade of cellular events such as cellular depolarization and Ca2+ influx, resulting in excitotoxic cell death. The critical determinant of severity of brain injury is the duration and severity of the ischemic insult and early restoration of CBF. Induced therapeutic hypothermia following CA is the only strategy that has demonstrated improvement in outcomes in prospective, randomized clinical trials. Although pharmacologic neuro-protection has been disappointing thus far in a variety of experimental animal models, further research efforts are directed at using some agents that demonstrate marginal or moderate efficacy in combination with hypothermia. Although the signal transduction pathways and intracellular molecular events during cerebral ischemia and reperfusion are complex, potential therapeutic neuroprotective strategies hold promise for the future.
Harukuni
Izumi
I
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Division of Cardiac Anesthesiology, Tower 711, Johns Hopkins Hospital, 600 N. Wolfe Street, Baltimore, MD 21287, USA.
Bhardwaj
Anish
A
D017209:Apoptosis / Q000502:physiology; D001224:Aspartic Acid / Q000378:metabolism; D001831:Body Temperature; D001921:Brain / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology*; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D015220:Calcium Channels / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism; D006710:Homocysteine / Q000378:metabolism; D006801:Humans; D009336:Necrosis / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D018091:Receptors, AMPA / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism
D015220:Calcium Channels; D016207:Cytokines; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D006710:Homocysteine; D001224:Aspartic Acid; D009569:Nitric Oxide; D004298:Dopamine; D009638:Norepinephrine