Buyang Huanwu Decoction enhances hippocampal-cortical connectivity remodeling via sonic hedgehog signaling to ameliorate memory dysfunction in cerebral ischemic rats.

Abstract

Background: Although Buyang Huanwu Decoction (BHD) has been shown to promote functional recovery of memory following ischemic stroke, the precise mechanisms underlying its therapeutic effects remain incompletely understood. This study aimed to investigate the impact of BHD on hippocampal-cortical connectivity and elucidate the associated neurobiological mechanisms mediating its restorative effects.

Methods: A permanent middle cerebral artery occlusion (MCAO) rat model was established to simulate ischemic stroke conditions for subsequent experimental analyses. MCAO rats received daily intragastric administration of BHD over a 30-day treatment period. Cognitive performance, specifically spatial learning and memory, was assessed using the Morris water maze (MWM) test. Structural alterations in the hippocampus and cortex were quantified through magnetic resonance imaging (MRI), while functional neuronal activity was evaluated using blood-oxygen-level-dependent (BOLD) imaging, including amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) analyses. Seed-based functional connectivity analysis derived from BOLD signals was employed to investigate dynamic changes in hippocampocortical connectivity. Additionally, the involvement of the Sonic hedgehog (Shh) signaling pathway was examined using Western blotting to elucidate potential molecular mechanisms underlying the therapeutic effects of BHD.

Results: Therapeutic administration of BHD significantly ameliorated ischemia-induced memory impairments, attenuated structural damage in hippocampal and cortical regions, and restored neuronal activity levels in the post-stroke hippocampal regions. Notably, BHD treatment promoted functional reorganization of hippocampal-cortical connectivity, concomitant with the modulation of the Shh signaling pathway in both hippocampal and cortical regions.

Conclusions: The treatment with BHD facilitated the remodeling of the connectivity between the hippocampus and cortex, and ultimately alleviated memory dysfunction following stroke. These findings hold great promise in promoting the development of BHD research and enhancing its clinical utility.