Electroacupuncture ameliorates cognitive impairment and white matter injury in vascular dementia rats via activating HIF-1α/VEGF/VEGFR2 pathway

Vascular dementia (VaD) significantly impairs patients' quality of life and imposes a major social and economic burden. Electroacupuncture (EA), a contemporary modification of traditional acupuncture, has demonstrated potential in improving cognitive function in VaD, particularly when applied at the Shenting and Baihui. However, the underlying mechanisms remain inadequately understood. Elucidating how EA ameliorates cognitive deficits is critical for validating its clinical application and advancing non-pharmacological interventions for neurodegenerative disorders. This study aimed to investigate the neuroprotective mechanisms of electroacupuncture at these acupoints on cognitive function in VaD rats. VaD was induced in male Sprague-Dawley rats through bilateral common carotid artery occlusion (BCAO), with sham rats serving as controls. Rats were subsequently divided into three groups: BCAO, BCAO + EA and BCAO + EA + YC-1 (a HIF-1α inhibitor). Electroacupuncture was applied to the Shenting and Baihui. Cerebral blood flow (CBF) was measured using dynamic susceptibility contrast functional MRI, and cognitive recovery was evaluated through the Morris water maze. Immunohistochemical analysis quantified myelin repair and angiogenesis, while expression of HIF-1α, VEGF and VEGFR2 in white matter was quantified using PCR and Western blot. The results indicated that electroacupuncture improved learning and memory, increased CBF, enhanced myelin recovery and promoted angiogenesis in VaD rats. The expression of HIF-1α, VEGF and VEGFR2 in the white matter was significantly elevated in VaD rats. Electroacupuncture at Shenting and Baihui activates the HIF-1α/VEGF/VEGFR2 pathway, enhances angiogenesis, white matter perfusion and myelin repair, thereby restoring cognitive function in VaD rats.