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

Young Dae Cho; Hyoung Soo Byoun; Kwang Hyon Park; Young Il Won; Jeongwook Lim

doi:10.1007/s12028-024-01980-w

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

Neurocrit Care. 2024 Apr 8. doi: 10.1007/s12028-024-01980-w. Online ahead of print.

Authors

Young Dae Cho¹, Hyoung Soo Byoun^{2

3}, Kwang Hyon Park², Young Il Won², Jeongwook Lim^{4

5}

Affiliations

¹ Department of Radiology, Seoul National University Hospital and Seoul National University College of Medicine, Seoul, Korea.
² Department of Neurosurgery, Chungnam National University Sejong Hospital, Sejong, South Korea.
³ Department of Neurosurgery, Chungnam National University School of Medicine, Daejeon, Korea.
⁴ Department of Neurosurgery, Chungnam National University Sejong Hospital, Sejong, South Korea. jeongwook.lim@gmail.com.
⁵ Department of Neurosurgery, Chungnam National University School of Medicine, Daejeon, Korea. jeongwook.lim@gmail.com.

PMID: 38589694
DOI: 10.1007/s12028-024-01980-w

Abstract

Background: Enteral nimodipine is the most evidence-based and widely used drug for the treatment of delayed cerebral ischemia 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).

Methods: SAH was experimentally introduced in white rabbits (n = 42) that were grouped as follows: enteral nimodipine (SAH-nimodipine group, n = 14), a control that received normal saline (SAH-saline group, n = 13), and a control without hemorrhage (control group, 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]).

Results: Cytoplasmic vacuolation of smooth muscle cells was observed in two SAH hemorrhagic groups and was more prominent in the SAH-saline group. Endothelial desquamation was observed only in the SAH-saline group. For the basilar artery, expression of Bcl2 and Bax in the SAH-nimodipine group was lower than that in the SAH-saline group, but significant differences were not observed (p^Bcl2 = 0.311 and p^Bax = 0.720, respectively). In penetrated arterioles, the expression of Bax in the SAH-nimodipine group was significantly lower than that of the SAH-saline group (p < 0.001). The thickness of the tunica media in the basilar artery was thinner in the SAH-nimodipine group than in the SAH-saline group (p < 0.001).

Conclusions: 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.

Keywords: Aneurysm; Apoptosis; Endothelium; Nimodipine; Subarachnoid hemorrhage.

Abstract

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