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.

钙敏感受体（CaSR）在脑缺血和脑外伤中的颠覆作用最近已有报道。然而，CaSR在蛛网膜下腔出血（SAH）后早期脑损伤（EBI）中的作用尚待探索。使用小鼠血管内穿孔模型，本研究旨在研究SAH后CaSR在EBI中的作用和潜在机制。腹膜内施用CaSR的激动剂三氯化（GdCI3）和CaSR的抑制剂NPS-2143。将CaMKII抑制剂KN-93注射到脑室内。我们发现，SAH后CaSR表达增加并在神经元，星形胶质细胞和小胶质细胞中广泛表达。GdCI3进一步恶化了神经功能，脑水肿，神经退行性变，这被NPS-2143缓解。也，GdCI3增加了CaMKII磷酸化水平，并上调了NRP-2143减弱的NLRP3，裂解的caspase-1和IL-1β的表达。此外，CaMKII抑制剂KN-93下调了GdCl3诱导的NLRP3，裂解的caspase-1和IL-1β的表达。总之，CaSR激活可促进早期脑损伤，这可能与CaMKII / NLRP3信号通路有关。