title: Therapeutic effect of tirilazad mesylate (U-74006F), mannitol, and their combination on experimental ischemia.
abstract: The effect of tirilazad mesylate (U-74006F), mannitol, and their combination was investigated on focal cerebral ischemia induced by permanent middle cerebral artery (MCA) occlusion in rabbits. Rabbits were divided into four groups receiving vehicle, U-74006F, mannitol, and U-74006F plus mannitol. Hematocrit (hct), glucose, mean arterial blood pressure (MABP), pH, PCO2, and PO2 were measured both before and after occlusion. Seventy-two hours following the permanent MCA occlusion, the neurological outcome was assessed and a quantitative neuropathologic examination was performed in all rabbits. The neurological outcome was better in the rabbits treated with U-74006F plus mannitol than in the other groups. The size of infarction of the affected hemisphere following MCA occlusion was 49.7% in the control group, 30.6% in the U-74006F group, 47.6% in the mannitol group, and 24.1% in the U-74006F plus mannitol group. There was a statistically significant reduction in infarct size in the U-74006F plus mannitol group compared with the other groups (P < 0.05). The ratio of ischemic neurons to total neurons in the cortex was smaller in the U-74006F plus mannitol group than in the other groups. The ratio of ischemic neurons to total neurons in the subcortex was significantly lower in the U-74006F plus mannitol group than in the other groups (P < 0.05). Our data provide evidence for the beneficial effects of both U-74006F and U-74006F plus mannitol in promoting neurological recovery and preservation of the ischemic area.
authors.affiliation: Department of Neurosurgery, Erciyes University Medical School, Kayseri, Turkey.
authors.forename: I S
authors.initials: IS
authors.lastname: Oktem
authors.forename: A
authors.initials: A
authors.lastname: Menkü
authors.forename: H
authors.initials: H
authors.lastname: Akdemir
authors.forename: O
authors.initials: O
authors.lastname: Kontaş
authors.forename: A
authors.initials: A
authors.lastname: Kurtsoy
authors.forename: R K
authors.initials: RK
authors.lastname: Koç
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004234:Diuretics, Osmotic / Q000494:pharmacology / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D008353:Mannitol / Q000494:pharmacology / Q000627:therapeutic use*; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D010784:Photomicrography; D011281:Pregnatrienes / Q000494:pharmacology / Q000627:therapeutic use*; D011817:Rabbits; D011897:Random Allocation; D018709:Statistics, Nonparametric
chemical_list: D004234:Diuretics, Osmotic; D018696:Neuroprotective Agents; D011281:Pregnatrienes; D008353:Mannitol; C053355:tirilazad