Remote Ischemic Postconditioning Protects the Neurovascular Units in MCAO/R Rats through HIF-1α-Mediated Pathway

Abstract

Remote ischemic postconditioning (RIPostC), administered after the onset of local ischemia, has been shown to have beneficial effects on neurological, vascular, and motor functions in animal models. However, the precise mechanisms and interactions underlying these functional improvements remain unclear. Our study aimed to determine whether RIPostC exerts protective effects on the neurovascular units (NVU) and to investigate whether this protection is mediated by hypoxia-inducible factor-1α (HIF-1α). We used left middle cerebral artery occlusion and reperfusion (MCAO/r) to induce ischemic stroke in rats and applied RIPostC. YC-1 was used to inhibit the activity of HIF-1α. Following the 12-day RIPostC treatment, MRI scans showed a significant reduction in infarct volume in the affected area, accompanied by an increase in HIF-1α protein levels and its downstream angiogenic factors in the ischemic zone. Additionally, RIPostC promoted angiogenesis in the ischemic penumbra, which, in turn, reduced neuronal loss and astrocyte activation. Behavioral assessments further indicated that RIPostC treatment partially restored the motor function in MCAO/r rats. However, the therapeutic effects of RIPostC were counteracted by the addition of YC-1, suggesting that the protective effects of RIPostC against NVU are mediated through HIF-1α. Overall, our research demonstrates that RIPostC is an effective rehabilitative intervention for protecting NVU in MCAO/r rats through the HIF-1α-mediated pathway.