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 (MgSO4) can protect cells by modulating the intracellular Ca2+ content in damaged cells, suggesting that they could be hypothermia infusion solution. In this study, we hypothesized that MgSO4, 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 MgSO4 treatment on different neurovascular (NVU) cells after oxygen-glucose deprivation/reoxygenation (OGD/R) injury was examined. Results: Compared with the IA-SCSI or IA-MgSO4 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 MgSO4 provided maximum protection to the NVU cells, and this protective effect was mainly achieved through the regulation of Ca2+ homeostasis in different cells. Conclusion: MgSO4 may be a promising hypothermia infusion solution to facilitate the recovery of neurological function in AIS patients.