Neuroprotective effects of hypothermia and U-78517F in cerebral ischemia are due to reducing oxygen-based free radicals: an electron paramagnetic resonance study with gerbils.
Free radicals are implicated as causative agents in various forms of tissue destruction. Considerable circumstantial evidence suggests that oxygen-based free radicals generated as blood flow returns to formerly ischemic brain areas are mainly responsible for the neurodegeneration that follows periods of cerebral ischemia. In general, oxygen-based free radicals are highly reactive and exist for only a brief period of time. This makes the direct measurement of many of these free radicals rather difficult. Much of the current knowledge of free radicals in cerebral ischemia is based on observations of chemical changes brought about by the free radicals rather than on direct observations of the free radicals themselves. Low temperature electron paramagnetic resonance spectroscopy is one method that allows the direct study of free radicals. Compared to samples from sham-operated controls, samples of hippocampus taken from gerbils exposed to 15 min of forebrain ischemia followed by 15 min of reperfusion, frozen in liquid nitrogen less than 20 sec after sacrifice, and scanned by low temperature (100 K) electron paramagnetic resonance, show a significant increase in oxygen-based free radicals and a decrease in carbon-based ubiquinone-like free radicals. The ischemia-induced increase in oxygen-based free radicals is prevented by the intraperitoneal injection of the antioxidant drug U-78517F at the start of reperfusion and by hypothermia. However, neither intervention alters the ischemia-induced reduction in the ubiquinone-like free radicals. This suggests that the neuroprotective actions of hypothermia and U-78517F include a direct reduction in the oxygen-based free radical burden of the post-ischemic tissue.
Zhao
W
W
Department of Pharmacology, University of Saskatchewan, Saskatoon, Canada.
Richardson
J S
JS
Mombourquette
M J
MJ
Weil
J A
JA
Ijaz
S
S
Shuaib
A
A
D000818:Animals; D001923:Brain Chemistry / Q000502:physiology; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D002839:Chromans / Q000008:administration & dosage / Q000627:therapeutic use*; D004578:Electron Spin Resonance Spectroscopy; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000627:therapeutic use*; D005849:Gerbillinae; D007036:Hypothermia, Induced; D007274:Injections, Intraperitoneal; D008297:Male; D010879:Piperazines / Q000008:administration & dosage / Q000627:therapeutic use*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015427:Reperfusion Injury / Q000473:pathology / Q000628:therapy
D002839:Chromans; D016166:Free Radical Scavengers; D010879:Piperazines; D017382:Reactive Oxygen Species; C066382:U 78517F