Ferrous Chelator 2,2′-Dipyridyl Attenuates Cerebral Vasospasm after Experimental Subarachnoid Haemorrhage in Rabbits

Abstract

The effect of 2,2'-dipyridyl (DP) on cerebral vasospasm was investigated in a doubleinjection rabbit model of subarachnoid haemorrhage (SAH). Thirty-six animals were divided between four groups: control (sham-operated), SAH (model alone), SAH + DP (the SAH model in which DP dissolved in dimethyl sulphoxide [DMSO] was injected once daily for 5 days into the cisterna magna), and SAH + DMSO (the SAH model in which DMSO [vehicle] was injected daily for 5 days). There were significant differences in the basilar artery luminal area, wall thickness, neurological deficit score and vasospasm index between the SAH + DP and SAH groups. There was a significant negative correlation between arterial luminal area and arterial wall thickness, and also between the neurological deficit score and vasospasm index. Cells that were positive for terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick endlabelling (TUNEL) and p53 expression were significantly increased in the SAH + DMSO and SAH groups, but not in the SAH + DP group, versus controls. Thus, DP may attenuate cerebral vasospasm after SAH by suppressing p53-induced apoptosis in the cerebral vessels.

Efficacy of the lipid-soluble iron chelator 2,2′-dipyridyl against hemorrhagic brain injury

“…Lipid-soluble ferrous iron chelator 2,2′-dipyridyl (DP) has been reported to alleviate brain damage in different rodent models of cerebral ischemia (Demougeot et al, 2004; Methy et al, 2008; Millerot-Serrurot et al, 2008; Van Hoecke et al, 2005) and to reduce cerebral vasospasm in primate and rabbit models of subarachnoid hemorrhage (Horky et al, 1998; Yu et al, 2010). The lipid solubility of DP is evidenced by its ability to freely enter brain cells and chelate intracellular free iron, thereby reducing iron-induced cell death (Breuer et al, 1995; Kress et al, 2002; Methy et al, 2008).…”