SYSTEMIC ADMINISTRATION OF THE IRON CHELATOR DEFERIPRONE ATTENUATES SUBARACHNOID HEMORRHAGE-INDUCED CEREBRAL VASOSPASM IN THE RABBIT

OBJECTIVE: Iron catalyzed generation of injurious free radicals has be en implicated in the pathogenesis of cerebral vasospasm after subarach noid hemorrhage (SAH). The present study assessed the effects of the i ron chelator deferiprone on cerebral vasospasm in an in vivo rabbit mo del of SAH. METHODS: Twenty-four rabbits were ar signed to three group s as follows: SAH plus placebo (n = 8), SAH plus deferiprone (n = 8), or control plus placebo (n = 8). Deferiprone was administered to an ad ditional group of three rabbits that were not subjected to SAH. Drug a dministration was initiated 8 hours after SAH was induced and was repe ated at 8-hour intervals. The animals were killed using perfusion-fixa tion 48 hours after SAH. Cross-sectional areas of basilar artery histo logical sections were measured by an investigator blinded to the treat ment groups. RESULTS: In placebo-treated animals, the average luminal cross-sectional area of the basilar artery was reduced by 54% after SA H compared to controls. (i.e., from 0.272 to 0.125 mm(2)). The vasospa stic response after SAH was attenuated significantly in animals treate d with deferiprone (0.208 mm(2), representing a 24% reduction). CONCLU SION: Previous experimental studies suggested that iron chelation can be effective in attenuating cerebral vasospasm after SAH. Deferiprone is a recently developed iron chelator that has been extensively evalua ted for the treatment of patients requiring chronic blood transfusions . The present study demonstrates that deferiprone is effective in atte nuating experimental cerebral vasospasm. Because of its stability, lip ophilicity, and ability to penetrate the blood-brain barrier, deferipr one represents an attractive candidate for the treatment of cerebral v asospasm.