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

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.

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

A photothrombotic stroke mouse model was established. Neurological function and infarct volume were assessed following BYHWD treatment. Nestin^CreERT2/+; Rosa^tdTomato/+ 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.

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.

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