Extracellular vesicles from medicated plasma of Buyang Huanwu decoction-preconditioned neural stem cells accelerate neurological recovery following ischemic stroke

Abstract

<p><strong>Introduction:</strong> The neurological impairment of survivors after ischemic stroke poses a serious risk to their quality of life and health. Effective therapeutic options are still lacking. Neural stem cells (NSCs) promote neurogenesis <em>via</em> secreted extracellular vesicles (NSC-EVs), which would be a potential therapeutic option, but the insufficient quantity of NSC-EVs <em>in vivo</em> restrains clinical application. Buyang Huanwu Decoction (BHD), a classic traditional Chinese medicine (TCM) decoction, is promising to alleviate neurological impairment after ischemic stroke. It was speculated that BHD might promote neurological recovery through the NSC-EVs.</p><p><strong>Methods:</strong> The medicated plasma of BHD (MP-BHD) was prepared to precondition NSCs and isolate EVs (BHD-NSC-EVs). Middle cerebral artery occlusion (MCAO) models and primary NSCs were administered to evaluate the therapeutic effect. Next-generation sequencing was performed to explore the mechanism.</p><p><strong>Results:</strong> The BHD-NSC-EVs more significantly accelerated neurological recovery after MCAO and promoted NSCs proliferation and differentiation than BHD and NSC-EVs alone. MP-BHD enhanced the largescale generation of BHD-NSC-EVs, which encapsulated functional miRNA and may play critical roles in neurogenesis.</p><p><strong>Discussion:</strong> In replacing BHD or NSCs, the preconditioned NSC-EVs present a more efficient therapeutic strategy for ischemic stroke. Based on the clinical efficacy of TCM, the preconditioning of NSC-derived EVs <em>via</em> the MP of TCM herbs would presents a newly promising therapeutic strategy for neurological diseases.</p>