Effect of tirilazad mesylate given after permanent middle cerebral artery occlusion in rat.

Abstract

The effect of the antioxidant drug tirilazad mesylate (U-74006F) on histopathological and neurological outcome 3 days after permanent middle cerebral artery (MCA) occlusion was evaluated in rats. Several previous studies have demonstrated the efficacy of tirilazad in reducing infarct size when administered before and during MCA occlusion, whereas post-treatment may be less effective in permanent focal ischaemia. We sought to determine if a protective effect of tirilazad could be demonstrated when administered after the insult only. U-74006F (3 mg/kg, i.v.) or sterile vehicle, was randomly given to rats 10 minutes and 3 hours after permanent MCA occlusion produced by transcranial proximal electrocauterization. Infarct volume and hemisphere volumes were estimated blindly from histological sections of defined levels of the brain after 72 h of ischaemia. Neurological score was determined blindly 1, 2, and 3 days after insult. There was no significant difference in infarct volume, volume of non-infarcted tissue, or neurological score between the tirilazad and placebo-treated rats. In conclusion, our results support the conception that post-treatment with tirilazad mesylate is not efficacious in reducing infarct size in permanent focal ischaemia, while pre-treatment, as reported by other groups, appears to be effective in both permanent and temporary focal ischaemia models. In temporary focal ischaemia, the limited data available suggest that also post-treatment with tirilazad may prove to be neuroprotective.