Efficacy of Low-Intensity Transcranial Ultrasound Stimulation in Enhancing Motor Recovery via Modulation of Microglial Polarization, Angiogenesis and Neurogenesis in MCAO Rats

Low-intensity transcranial ultrasound stimulation (LITUS) is a novel neuromodulation technology characterized by its non-invasive nature, strong penetration, and high spatial resolution, which has been applied in the treatment of neurological diseases. LITUS has demonstrated effectiveness in promoting motor function recovery following stroke; however, the underlying mechanisms remain unclear. A rat model of middle cerebral artery occlusion (MCAO) was established using the suture method, followed by a 6-day LITUS intervention initiated 24 h postmodel creation. The motor function of MCAO rats was evaluated using the open field test, catwalk gait analysis, and beam walking test. Additionally, a 9.4T animal MRI was employed to assess cerebral infarction volume and edema. Molecular biological changes related to microglial polarization, angiogenesis and neurogenesis were evaluated using enzyme-linked immunosorbent assay and immunofluorescence staining. LITUS treatment significantly attenuated ischemic brain injury and improved motor dysfunction in MCAO rats. We observed that MCAO induced microglial activation and polarization in the ischemic brain cortex. Conversely, LITUS treatment inhibited microglial activation, suppressed M1 microglial polarization, and enhanced M2 microglial polarization. Furthermore, LITUS treatment promoted angiogenesis and neurogenesis in the brains of MCAO rats. LITUS treatment effectively improves motor dysfunction in MCAO rats, potentially through the regulation of microglial polarization and the promotion of angiogenesis and neurogenesis. Therefore, LITUS may represent a promising therapeutic approach for addressing motor recovery associated with ischemic stroke.