ALPHA-PHENYL-TERT-BUTYL-NITRONE REDUCES CORTICAL INFARCT AND EDEMA IN RATS SUBJECTED TO FOCAL ISCHEMIA

The neuroprotective effects of the spin-trapping agent alpha-phenyl-N-tert-butyl nitrone (PBN) were evaluated in rats subjected to focal cerebral ischemia produced by permanent middle cerebral artery (MCA) and ipsilateral common carotid artery (CCA) occlusion. PBN was given i.p. at 100 mg/kg at initial times of administration of 0.5 h prior to ischemia (group 2), 0.5 (group 3), 5 (group 4) and 12 h (group 5) after ischemia. Additional doses of PBN (100 mg/kg) were administered as follows: Group 2, at 24 h; Group 3, at 5, 17, 29 and 41 h; Group 4, at 17, 29 and 41 h; Group 5, at 24 and 36 h. Animals were sacrificed 48 h after MCA occlusion and infarct volumes were calculated from triphenyltetrazolium stained 1.5 mm slices of the forebrain. PBN significantly attenuated cortical infarct volume and cerebral edema in all of the treated rats compared with those in ischemic control (group 1) rats, with no significant differences between the different PBN treated groups. The percentage of infarct volume in ischemic control rats was 22.7 +/- 1.0, while those in PBN-treated groups were: 9.6 +/- 2.0, P < 0.01 (group 2); 12.2 +/- 2.2, P < 0.01 (group 3); 11.1 +/- 2.9, P < 0.01 (group 4) and 14.4 +/- 2.5, P < 0.01 (group 5). Furthermore, neurological behavior tests showed that PBN decreased the neurological deficit scores in rats initially treated either prior to or for up to 12 h after ischemia. These finding demonstrate that PBN has a strong neuroprotective effect, supporting the hypothesis that the free radicals play an important role in brain injury following cerebral ischemia and suggest that PBN could have potential therapeutic value for the treatment of ischemic stroke.