The ferric iron chelator 2,2'-dipyridyl attenuates basilar artery vasospasm and improves neurological function after subarachnoid hemorrhage in rabbits.

ABSTRACT

We investigated the efficacy of the ferrous iron (Fe(2+)) chelator 2,2'-dipyridyl (DP) to attenuate cerebral vasospasm after subarachnoid hemorrhage (SAH). Thirty-six New Zealand white rabbits were randomly assigned to four groups untreated control, SAH, SAH + dimethyl sulfoxide (DMSO) vehicle, and SAH + DP. SAH was induced by injection of autologous blood into the cisterna magna and then DP or vehicle was infused into the cistern magna for 5 days (20 mg/kg/day or an equal volume of DMSO). Neurological deficit score (NDS) was used to assess neurological function and cerebral angiography to measure basilar artery (BA) diameter following SAH. TUNEL staining was used to detect BA endothelial cell apoptosis, and immunohistochemistry and Western blotting to assess changes in caspase-3 protein levels 5 days post-SAH. The SAH + DP group had a significantly larger mean BA diameter and lower mean NDS post-SAH compared to the SAH + DMSO and SAH groups (p < 0.05). TUNEL-positive cell numbers and caspase-3 levels were significantly reduced in BA endothelial cells of the SAH + DP group as compared to the SAH and SAH + DMSO groups (p < 0.05). The iron chelator DP reduced vasospasm and neurological sequelae in rabbits, likely by chelating the Fe(2+) in oxyhemoglobin and reducing oxidative stress-induced endothelial cell apoptosis.