Role of Cyclooxygenase-2 in Relation to Nitric Oxide and Endothelin-1 on Pathogenesis of Cerebral Vasospasm After Subarachnoid Hemorrhage in Rabbit

Abstract

Endothelial dysfunctions that include decreased nitric oxide (NO) bioactivity and increased endothelin-1 (ET-1) bioactivity have been considered to be involved in the pathogenesis of cerebral vasospasm (CVS) after aneurysmal subarachnoid hemorrhage (SAH). Recent cardiovascular studies have revealed that cyclooxygenase-2 (COX-2) is involved in a disturbance in cross-talk between NO and ET-1. COX-2 expression was detected in the endothelial cells of a spastic artery after experimental SAH; however, the pathophysiological significance of COX-2 in relation to CVS remains unclear. The aim of this study was to investigate the role of COX-2 in relation to NO and ET-1 in the pathogenesis of CVS by using the COX-2 selective inhibitor, celecoxib. In the SAH group, SAH was simulated using the double-hemorrhage rabbit model. In the celecoxib group, SAH was simulated and celecoxib was administered. The basilar artery was extracted on day 5 and examined. The cross-section area of the basilar artery in the celecoxib group was significantly larger than in the SAH group. An increased expression of COX-2, ET-1, and ETA receptor (ETAR), and a decreased expression of endothelial NO synthase (eNOS) were seen in the SAH group. In the celecoxib group compared to the SAH group, expression of COX-2, ET-1, and ETAR were statistically significantly decreased, and eNOS expression was significantly increased. COX-2 might be involved in the pathogenesis of CVS due to up-regulation of ET-1 and ETAR and down-regulation of eNOS, and celecoxib may potentially serve as an agent in the prevention of CVS after SAH.

Regulation of Hypertension for Secondary Prevention of Stroke: The Possible ‘Bridging Function' of Acupuncture

“…EA to the bilateral ST36 acupoints for 20 min in SIHRs induced nitric oxide (NO) in the ventral periaqueductal gray matter (vPAG) due to activation of the sympathetic inhibitory system [36]. NO has been suggested to mitigate the cerebral vasospasm [37]. EA plus running could increase the levels of neuropeptide Y, neurokinin A, and substance P in the hippocampus [38].…”

“…Ang II was involved in apoptosis, inflammation [81], the neurological deficit score, hemorrhage volume [82], hypertrophy, and inward remodeling of cerebral arterioles [83]; after decreasing the Ang II levels, cerebral blood supply was improved [84], and ET-1 may promote the development of the stroke process [85]. ETAR and NO may be involved in the pathogenesis of cerebral vasospasm [37]. Acupuncture with the twirling reducing method at the left LR3 increased the calcitonin gene-related peptide (CGRP) levels in the blood plasma and the hypothalamus of rats [86].…”

Anti-high mobility group box-1 (HMGB1) antibody attenuates delayed cerebral vasospasm and brain injury after subarachnoid hemorrhage in rats

“…Munakata and their collaborators demonstrated that the down-regulated expression of the eNOS gene in the BA of SAH rabbits was almost completely recovered by using the cyclooxygenase-2 (COX-2) selective inhibitor, suggesting the involvement of arachidonic acid metabolites in delayed vasospasm after SAH42. Thus, reduction of NO production by eNOS after SAH appeared to be mediated by COX-2 metabolites but not HMGB1.…”

Salvinorin A ameliorates cerebral vasospasm through activation of endothelial nitric oxide synthase in a rat model of subarachnoid hemorrhage

“…The neuronal damage and endothelial damage could happen simultaneously, which results in the disruption of neurovascular unit, the increase in permeability, and edema formation in SAH. Neurovascular unit impairment after SAH has been reported to correlate with the development of cerebral vasospasm . SA could potentially protect both the endothelial and neuronal cells through similar mechanisms.…”