The Impact of Enteral Nimodipine on Endothelial Cell Apoptosis in an Animal Subarachnoid Hemorrhage Model

Abstract

Abstract Objective: Enteral nimodipine is the most evidence-based and widely used drug for the treatment of delayed cerebral ischemia (DCI) and is known to have various neuroprotective functions. However, the neuroprotective mechanism of nimodipine still remains unclear and the effects of nimodipine remain ambiguous. Herein, we studied the effect of enteral nimodipine on endothelial apoptosis after subarachnoid hemorrhage (SAH). Method: SAH was experimentally introduced in white rabbits (n=42) that were grouped: enteral nimodipine (group N, n=14); a control that received normal saline (group S, n=13); and a control without hemorrhage (group C, n=15). On the third day after SAH induction, the brain stem, including the vertebrobasilar vascular system, was extracted. The effects of enteral nimodipine were analyzed by group using histopathologic analysis, including immunohistochemical staining of apoptosis-related proteins (Bcl2 [anti-apoptotic] and Bax [pro-apoptotic]). Result: Cytoplasmic vacuolation of smooth muscle cells was observed in groups S and N, and was more prominent in group S. Endothelial desquamation was observed only in group S. For the basilar artery, expression of Bcl2 and Bax in group N was lower than in group S, but significant differences were not observed (p = 0.310 and p = 0.710, respectively). In penetrated arterioles, the expression of Bax in group N was significantly lower than that of group S (p < 0.001). The thickness of the tunica media in the basilar artery was thinner in group N than in group S (p < 0.001). Conclusion: This study suggests that enteral nimodipine may have a neuroprotective function by inhibiting endothelial apoptosis in small arterioles and preventing smooth muscle cell proliferation in large arteries.