Whole-Body Vibration Promotes Neurological Recovery From Subarachnoid Hemorrhage via Meningeal Lymphatic Drainage and CD4Treg-Mediated Immunomodulation.

Abstract

BACKGROUND: Whole-body vibration (WBV) has emerged as a promising non-pharmacological intervention for chronic neurological disorders; however, its underlying mechanisms remain incompletely understood. In this study, we investigated the therapeutic efficacy and mechanistic basis of WBV in subarachnoid hemorrhage (SAH), a severe condition characterized by high mortality and long-term neurological deficits. METHODS: SAH was induced in mice via chiasmatic cistern injection. WBV intervention (frequency: 28 Hz, amplitude: 0.3 mm) was initiated 7 days post-SAH and continued for 3 consecutive weeks. Neurological function was assessed using the open field test, Morris water maze, Y-maze, and gait analysis. Meningeal lymphatic vessel (MLV)-mediated drainage was evaluated throughfluorescence imaging of Evans blue and Alexa Fluor 647-conjugated ovalbumin clearance. The expression of podoplanin () and lymphatic vessel endothelial hyaluronan receptor 1 (), specific markers of meningeal lymphatic endothelial cells, was analyzed in MLVs and deep cervical lymph nodes (dCLNs) using quantitative real-time polymerase chain reaction (qRT-PCR). Peripheral immunomodulatory changes were assessed by quantifying cluster of differentiation 4 and forkhead box protein P3 positive (CD4Foxp3) regulatory T cells (Tregs) in peripheral blood mononuclear cells via flow cytometry. RESULTS: WBV treatment significantly improved learning and memory deficits, emotional disturbances, and motor dysfunction in SAH mice. Mechanistically, WBV enhanced the drainage capacity of MLVs by promoting lymphangiogenesis. Furthermore, WBV increased the proportion of peripheral Tregs, indicating an enhanced immunomodulatory effect. CONCLUSIONS: This study demonstrates that WBV facilitates neurological recovery post-SAH by enhancing meningeal lymphatic drainage and expanding the peripheral Treg population. These findings highlight WBV as a promising, non-invasive therapeutic strategy for SAH rehabilitation.