Evidence for free radical mechanisms of brain injury resulting from ischemia/reperfusion-induced events.
Free radicals have been implicated in the injury that occurs to brain tissue in response to ischemia and reperfusion insults. Confirmatory in vivo studies have been limited by the difficulty in measuring free radicals in brain tissue. This review discusses potential mechanisms for free radical production in brain tissue and the evidence supporting the therapeutic efficacy of free radical scavengers. Free radicals may be produced during ischemia/reperfusion as a result of multiple mechanisms involving normal regulatory systems of intra-/extracellular metabolism. For example, metabolism of free fatty acids by the cyclo-oxygenase pathway and adenine nucleotides by xanthine oxidase has been proposed to produce free radical adducts during reperfusion. Therapeutic strategies aimed at decreasing brain injury from free radical production include administration of free radical scavengers at the time of reperfusion. Pharmacologic interventions for protection from free radical injury in brain are hindered because of limited access to the site of free production.
Kirsch
J R
JR
Department of Anesthesiology/Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Helfaer
M A
MA
Lange
D G
DG
Traystman
R J
RJ
D000818:Animals; D001921:Brain / Q000378:metabolism*; D001930:Brain Injuries / Q000503:physiopathology*; D002545:Brain Ischemia / Q000503:physiopathology*; D003676:Deferoxamine / Q000627:therapeutic use; D016166:Free Radical Scavengers; D005609:Free Radicals; D007962:Leukocytes / Q000502:physiology; D015427:Reperfusion Injury / Q000503:physiopathology* / Q000517:prevention & control; D014810:Vitamin E / Q000627:therapeutic use
D016166:Free Radical Scavengers; D005609:Free Radicals; D014810:Vitamin E; D003676:Deferoxamine