Store-operated Ca²⁺ entry (SOCE) contributes to Ca²⁺ refilling of endoplasmic reticulum (ER), but also provides Ca²⁺ influx involved in physiological and pathological signalling functions. Upon depletion of Ca²⁺ store, the sensor protein stromal interaction molecule (STIM) activates Orai1, forming an ion-conducting pore highly selective for Ca²⁺. SOCE-associated regulatory factor (SARAF) associates with STIM1 to facilitate a slow form of Ca²⁺-dependent inactivation of SOCE or interacts with Orai1 to stimulate SOCE in STIM1-independent manner. We have investigated whether cerebral ischemic damage and neuroprotection conferred by ischemic preconditioning (PC) in mouse are associated with changes in the expression of the molecular components of SOCE.

Ischemic PC induced by 15-min occlusion of the middle cerebral artery (MCAo) resulted in significant amelioration of histological and functional outcomes produced, 72 h later, by a more severe ischemia (1 h MCAo). Neither ischemia, nor PC affected the expression of Orai1 in the frontoparietal cortex. However, the number of Orai1-immunopositive cells, mostly corresponding to Ly-6G+ neutrophils, was significantly elevated in the blood after the ischemic insult, regardless of previous PC. The expression of Stim1 and SARAF, mainly localised in NeuN-immunopositive neurons, was reduced in the ischemic cortex. Interestingly, neuroprotection by ischemic PC prevented the reduction of SARAF expression in the lesioned cortex and this could be interpreted as a compensatory mechanism to restore ER Ca²⁺ refilling in neurons in the absence of STIM1. Thus, preventing SARAF downregulation may represent a pivotal mechanism implicated in neuroprotection provided by ischemic PC and should be exploited as an original target for novel stroke therapies.

储存操作的 Ca ²⁺进入 (SOCE) 有助于内质网 (ER) 的Ca ²⁺再填充，但也提供参与生理和病理信号功能的Ca ^2+流入。在 Ca ²⁺储存耗尽后，传感器蛋白基质相互作用分子 (STIM) 激活 Orai1，形成对 Ca ²⁺具有高度选择性的离子传导孔。SOCE 相关调节因子 (SARAF) 与 STIM1 结合以促进缓慢形式的 Ca ²⁺SOCE的依赖性失活或与Orai1相互作用以不依赖于STIM1的方式刺激SOCE。我们研究了小鼠缺血预处理 (PC) 赋予的脑缺血性损伤和神经保护是否与 SOCE 分子成分的表达变化有关。

由大脑中动脉 (MCAo) 闭塞 15 分钟诱导的缺血性 PC 导致 72 小时后由更严重的缺血 (1 小时 MCAo) 产生的组织学和功能结果显着改善。缺血和 PC 均不影响额顶叶皮层中 Orai1 的表达。然而，无论以前的 PC 情况如何，缺血性损伤后血液中的 Orai1 免疫阳性细胞数量（主要对应于 Ly-6G+ 中性粒细胞）显着升高。Stim1 和 SARAF 的表达主要位于 NeuN 免疫阳性神经元中，在缺血皮层中的表达降低。有趣的是，缺血性 PC 的神经保护阻止了受损皮质中 SARAF 表达的降低，这可以解释为恢复 ER Ca ^{2+的补偿机制}在没有 STIM1 的情况下重新填充神经元。因此，防止 SARAF 下调可能代表了与缺血性 PC 提供的神经保护有关的关键机制，应将其作为新中风治疗的原始目标。