Electroacupuncture improves hypoxic stress and energy metabolism to alleviate vascular cognitive impairment through activation of the HIF-1α/p53/NGB signaling pathway in rats.

Objectives: We aimed to demonstrate that electroacupuncture (EA) alleviates vascular cognitive impairment (VCI) induced by cerebral ischemia in rats by modulating oxygen homeostasis and energy metabolism through the HIF-1α/p53/NGB signaling pathway. Materials and Methods: Male Sprague‒Dawley rats underwent bilateral common carotid artery occlusion (BCCAO) to establish a VCI model. EA was administered once daily for 30 min over two weeks. Thirty minutes prior to EA, the hypoxia-inducible factor-1α (HIF-1α) inhibitor 2-methoxyestradiol (2ME2) was injected intraperitoneally. Cognitive function following BCCAO and EA was assessed using the Morris water maze test. Western blotting was performed to analyze the protein expression of HIF-1α, heme oxygenase-1 (HO-1), and neuroglobin (NGB). In addition, p53 mRNA expression was quantified by real-time PCR, and energy metabolite levels were determined using ELISA. Results: EA significantly improved learning and memory in VCI model rats. Histopathological analysis revealed that EA attenuated neuronal apoptosis and ultrastructural damage in the cortex and hippocampus. EA upregulated HIF-1α, NGB, and HO-1 expression but downregulated p53 mRNA expression in these regions. Moreover, EA treatment reversed the expression of glucose, lactic acid, and acetone aldehyde. Notably, the beneficial effects of EA on cerebral energy metabolism were abolished by 2ME2 in VCI model rats. Conclusion: EA alleviated BCCAO-induced neurological impairment and cognitive dysfunction in rats, possibly by reducing hypoxic stress and enhancing energy metabolism in the cortex and hippocampus, potentially through modulation of the HIF-1α/p53/NGB signaling pathway.