Buyang Huanwu Decoction Enhances SVZ-Lineage Neurogenic Responses Associated with β-catenin Signaling after Ischemic Stroke.

ETHNOPHARMACOLOGICAL RELEVANCE Ischemic stroke is a leading cause of death and disability, with limited therapies for neurological recovery. Buyang Huanwu Decoction (BYHWD) is a traditional Chinese medicine formula used for stroke, but its effects on endogenous neurogenesis and the underlying mechanisms remain incompletely defined.

Aim

OF THE STUDY This study investigated whether BYHWD promotes subventricular zone (SVZ)-derived neurogenesis after ischemic stroke and explored the involvement of β-catenin signaling.

Materials And Methods

A photothrombotic stroke mouse model was established. Neurological function and infarct volume were assessed following BYHWD treatment. NestinCreERT2/+; RosatdTomato/+ mice were used for lineage tracing of neural stem cells (NSCs) and their progeny. Short- and long-term neuronal differentiation was evaluated via immunofluorescence. SVZ transcriptomic analysis, Western blotting, immunofluorescence, and RT-qPCR were performed to assess β-catenin signaling. AAV-mediated β-catenin knockdown in NSCs was used to assess the functional involvement of β-catenin signaling.

Results

BYHWD improved neurological function and reduced infarct volume after stroke. Lineage tracing demonstrated that BYHWD increased SVZ-derived cells in the peri-infarct region, enhanced NSC proliferation and neuronal differentiation, and reduced astrocytic differentiation. At the long-term endpoint, BYHWD reduced the foot fault rate and increased the number of MAP2+tdTomato+ cells in the peri-infarct region. RNA sequencing revealed enrichment of Wnt/β-catenin signaling, while protein analyses showed increased levels of total and active β-catenin. RT-qPCR further demonstrated significant upregulation of the β-catenin target genes Axin2, Ccnd1, and Myc. β-catenin knockdown attenuated BYHWD-induced neurogenesis and functional recovery.

Conclusions

BYHWD promoted SVZ-derived neurogenesis after ischemic stroke, potentially through activation of β-catenin signaling.