Background
Studies consistently demonstrate that vascular cognitive impairment and dementia (VCID) onset and progression are associated with diminished activity in the Wnt/β-catenin signaling pathway, crucial for maintaining blood-brain barrier (BBB) integrity and promoting angiogenesis in the central nervous system. Transcutaneous auricular vagal nerve stimulation (taVNS) has shown potential to enhance cognitive function by reducing BBB permeability and stimulating angiogenesis, yet its direct linkage to the Wnt7/β-catenin pathway activation remains uncertain and requires mechanistic validation.
Methods
A rat model of VCID was established by inducing temporary bilateral common carotid artery occlusion (tBCCAO) in rats. Following surgery, rats received daily taVNS treatments for 14 consecutive days (Days 13–26). Cognitive function was assessed on postoperative day 26. Additionally, the hippocampal region was analyzed to detect changes in the Wnt7/β-catenin signaling pathway-related proteins, neuronal injury and apoptosis, angiogenesis, BBB tight junction integrity, and astrocyte activation.
Results
TaVNS treatment resulted in significant cognitive improvements, alongside marked reductions in neuronal damage and apoptosis within the hippocampal CA1 region. It effectively decreased BBB permeability and enhanced angiogenesis. Mechanistically, taVNS suppressed astrocyte activation, promoted a shift from pro-inflammatory (A1) to anti-inflammatory (A2) phenotypes, and consequently upregulated the Wnt7/β-catenin signaling pathway, boosting expression of its downstream targets to foster neuroprotection and vascular repair.
Conclusions
This study confirms that taVNS effectively alleviates neurological damage in VCID by upregulating the Wnt7/β-catenin pathway, potentially through astrocyte phenotypic modulation. These findings underscore taVNS as a promising non-invasive intervention for cognitive deficits in vascular disorders, warranting further clinical investigation.
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