Calcium sensing receptor contribute to early brain injury through the CaMKII/NLRP3 pathway after subarachnoid hemorrhage in mice.

The subversive role of Calcium sensing receptor (CaSR) in cerebral ischemia and traumatic brain injury has been recently reported. Nevertheless, the role of CaSR in early brain injury (EBI) after subarachnoid hemorrhage (SAH) remains unexplored. Using the endovascular perforation model in mice, this study was aimed at investigating the role and potential mechanism of CaSR in EBI after SAH. Gadolinium trichloride (GdCI3), an agonist of CaSR, and NPS-2143, an inhibitor of CaSR, were administered intraperitoneally. The CaMKII inhibitor KN-93 was injected to intracerebroventricular. We found that CaSR expression was increased and widely expressed in neurons, astrocytes, and microglia after SAH. GdCI3 further deteriorated neurological function, brain edema, neurodegeneration, which were alleviated by NPS-2143. Also, GdCI3 increased the level of CaMKII phosphorylation, and upregulated expression of NLRP3, cleaved caspase-1, and IL-1β, which were attenuated by NPS-2143. Besides, CaMKII inhibitor KN-93 down-regulated the upregulated expression of NLRP3, cleaved caspase-1, and IL-1β induced by GdCI3. In conclusion, CaSR activation promotes early brain injury, which may be related to the CaMKII/NLRP3 signaling pathway.