Role of Protease-Activated Receptor-1 in Brain Injury After Experimental Global Cerebral Ischemia

Abstract

Background Evidence suggests that the protease-activated receptor-1 (PAR-1), a thrombin receptor, mediates neuronal injury in experimental cerebral ischemia. The present study investigated whether PAR-1 plays a role in brain injury after global cerebral ischemia. Methods Adult male wild type (WT) or PAR-1 knockout mice underwent a 20-minute bilateral common carotid artery occlusion (BCCAO) or a sham operation. Behavior tests were performed before ischemia, and 1, 2 and 3 days after BCCAO. Mice were euthanized at different time points for thrombin activity, brain edema, Western blot analysis and brain histology. Results Thrombin activity and PAR-1 expression were increased in the brain after BCCAO. Compared with WT mice, PAR-1 knockout mice had less brain edema formation, neuronal death and behavior impairment after BCCAO. In addition, BCCAO-induced activation of mitogen-activated protein kinases was absent in PAR-1 knockout mice. Conclusion PAR-1 contributes to the brain injury induced by global cerebral ischemia, which may be related to activation of mitogen-activated protein kinases.

HO-1 Signaling Activation by Pterostilbene Treatment Attenuates Mitochondrial Oxidative Damage Induced by Cerebral Ischemia Reperfusion Injury

“…A reduction in mitochondrial complex I or IV activity may lead to mitochondrial respiratory chain deficiency and may result in ROS overproduction [34][35][36]. Compared with the IR group, PTE treatment significantly increased the MMP (Fig.…”

“…As described previously [34], right hemisphere and left hemisphere were obtained for further detection. Tissue samples were immediately weighed to obtain the wet weight.…”

“…As described previously [34], NeuN staining is used to mark viable neurons, and TUNEL staining is used to mark apoptotic cells. The number of NeuN-positive cells (Fig.…”

5-HMF attenuates striatum oxidative damage via Nrf2/ARE signaling pathway following transient global cerebral ischemia

“…Neuronal cell death is restricted to sensitive areas of brain, such as the striatum (Wang et al 2012;Yoshioka et al 2011a;Yoshioka et al 2011b). In this study, Cresyl violet and TUNEL staining carried out to detect brain damage revealed that the C57BL/6 mice model showed remarkable neuronal damage in the striatum after 24 h of reperfusion and 5-HMF significantly ameliorated pathological injury of the striatum.…”

“…The hippocampus receives much attention (Soares et al 2016;Takeuchi et al 2015), but the striatum has not been well studied. Evidence suggests that the striatal neurons are vulnerable to tGCI, as are hippocampal CA1 neurons, and tGCI produces consistent striatum injury (Wang et al 2012;Yoshioka et al 2011a;Yoshioka et al 2011b). The neuronal loss shows a close correlation with the deficits in neurological function, which are similar to clinic symptoms caused by neurological disorders, such as stroke (Ernst et al 2014;Lindvall and Kokaia 2006).…”