The nitroxide antioxidant tempol is cerebroprotective against focal cerebral ischemia in spontaneously hypertensive rats.
Free radicals appear to participate in the final common pathway of neuronal death in ischemia and may therefore be an adequate target for therapy. Tempol is a nitroxide antioxidant with proven protective efficacy in several animal models, including myocardial ischemia, that has not been previously tested in models of permanent cerebral ischemia. Spontaneously hypertensive rats underwent permanent middle cerebral artery occlusion (PMCAO). Following dose-response and time-window-finding experiments rats were given vehicle or tempol (50 mg/kg) subcutaneously 1 h after PMCAO (n = 10/group). Five animals in each group were evaluated with a motor scale 24 h after the infarct and were then sacrificed and the injury volume was measured. The remaining animals were examined daily with the motor scale and also with a Morris water maze test on days 26-30 after PMCAO and sacrificed on day 30. Motor scores at all time points examined were significantly better in the tempol-treated animals (P < 0.05 for all). Significantly better performance in the water maze test for performance on days 26-30 was noted in the tempol group compared with the vehicle-treated group (P < 0.05). Injury volumes at days 1 and 30 were significantly reduced in the tempol group (9.83 +/- 1.05 vs 19.94 +/- 1.43% hemispheric volume, P = 0.0009, and 13.2 +/- 2.97 vs 24.4 +/- 2.38% hemispheric volume, P = 0.02, respectively). In conclusion, treatment with tempol led to significant motor and behavioral improvement and reduced injured tissue volumes both in the short and in the long term after stroke.
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D001923:Brain Chemistry; D002545:Brain Ischemia / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D003497:Cyclic N-Oxides / Q000627:therapeutic use*; D004195:Disease Models, Animal; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D011918:Rats, Inbred SHR; D013113:Spin Labels; D016896:Treatment Outcome; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000032:analysis
D000975:Antioxidants; D003497:Cyclic N-Oxides; D018696:Neuroprotective Agents; D013113:Spin Labels; C002744:3-nitrotyrosine; D014443:Tyrosine; C001803:tempol