As. Arthur et al., SYSTEMIC ADMINISTRATION OF THE IRON CHELATOR DEFERIPRONE ATTENUATES SUBARACHNOID HEMORRHAGE-INDUCED CEREBRAL VASOSPASM IN THE RABBIT, Neurosurgery, 41(6), 1997, pp. 1385-1391
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.