Attenuation of Vascular Cognitive Impairment by Panaxadiol Through Promoting Hippocampal Angiogenesis in a Chronic Cerebral Hypoperfusion Model.

OBJECTIVE: This study explores the therapeutic efficacy and mechanisms of panaxadiol (PD), a ginseng-derived sapogenin, in a mouse model of vascular cognitive impairmentinduced by chronic cerebral hypoperfusion (CCH). METHODS: CCH was induced in C57BL/6 mice by bilateral common carotid artery stenosis (BCAS). Mice were assigned to Sham + normal saline (NS), Sham + PD, BCAS + NS or BCAS + PD groups. PD (50 mg/kg/d) or NS was administered orally for 30 days after surgery. Cerebral blood flow (CBF) was measured by laser speckle imaging at 1 h and 7, 14 and 30 d after BCAS. Cognitive function was assessed by behavioral tests, hippocampal angiogenesis by immunofluorescence staining and angiogenesis-related cytokines by protein array. RESULTS: PD restored CBF in BCAS mice by day 30 (p < .05 vs BCAS + NS), mitigated cognitive impairment, and increased hippocampal vascular density (p < .01) and new vessel formation (p < .0001). Neovascularisation showed significant or near-significant correlations with cognitive performance. PD decreased interferon gamma (IFN-γ) and tissue inhibitor of metalloproteinases 2 (TIMP-2) levels and increased vascular endothelial growth factor (VEGF) and tumor necrosis factor alpha (TNF-α) levels (all p < .05). In exploratory correlation analyses, newly formed vessel counts were negatively associated with IFN-γ and TIMP-2 and positively associated with VEGF and TNF-α. CONCLUSION: PD alleviated CCH-induced cognitive deficits and promoted hippocampal angiogenesis, accompanied by a shift toward a pro-angiogenic neurovascular microenvironment. These findings suggest that PD may support cognitive recovery in CCH by facilitating cerebrovascular repair and remodeling, although the precise mechanisms require further investigation.