MgSO4 as a novel hypothermia infusion solution promotes ischemic stroke recovery through Ca2+ regulation of neurovascular units

The neuroprotection of acute ischemic stroke (AIS) patients to alleviate the reperfusion injury is a long-standing problem. Although the intra-arterial selective cooling saline infusion (IA-SCSI) is a promising technique to improve the outcome of AIS, the clinical results are not sufficiently satisfactory. Magnesium-containing solutions such as magnesium sulfate (MgSO 4 ) can protect cells by modulating the intracellular Ca 2+ content in damaged cells, suggesting that they could be hypothermia infusion solution. In this study, we hypothesized that MgSO 4 , as a novel hypothermia infusion solution (IA-SCMI), can promote AIS recovery. Methods: First, IA-SCMI was performed in rats subjected to the middle cerebral artery occlusion. The effect of combined hypothermia and MgSO 4 treatment on different neurovascular (NVU) cells after oxygen-glucose deprivation/reoxygenation (OGD/R) injury was examined. Results: Compared with the IA-SCSI or IA-MgSO 4 infusion alone, IA-SCMI offered the best protective effect by improving neurological defects, and alleviating brain integrity damage and CBF reduction. Meanwhile, in vitro results revealed that the combination of hypothermia and MgSO 4 provided maximum protection to the NVU cells, and this protective effect was mainly achieved through the regulation of Ca 2+ homeostasis in different cells. Conclusion: MgSO 4 may be a promising hypothermia infusion solution to facilitate the recovery of neurological function in AIS patients.