【Abstract】
Transcranial focused ultrasound stimulation (tFUS) regulates neural activity in different brain regions in humans and animals. However, the role of ultrasound stimulation in modulating neural activity and promoting neurorehabilitation in the ischemic brain is largely unknown. In the present study, we explored the effect of tFUS on neurological rehabilitation and the underlying mechanism. Adult male ICR mice (n=42) underwent transient middle cerebral artery occlusion. One week after brain ischemia, low frequency (0.5 MHz) tFUS was applied to stimulate the ischemic hemisphere of mice for 7 consecutive days (10 minutes daily). Brain infarct volume, neurobehavioral tests, microglia activation, IL-10 and IL-10R levels were further assessed for up to 14 days. We found that the brain infarct volume was significantly reduced in the tFUS treated mice compared to that in the non-treated mice (p<0.05). Similarly, neurological severity scores, elevated body swing test, and corner test improved in the tFUS treated mice (p<0.05). We also demonstrated that tFUS resulted in increased M2 microglia in the ischemic brain region. The expression of IL-10R and IL-10 levels were also substantially upregulated (p<0.05). We concluded that tFUS served as a unique technique to promote neurorehabilitation after brain ischemia by promoting microglia polarization and further regulating IL-10 signaling in the ischemic brain.
【中文摘要】
經顱聚焦超聲刺激（tFUS）可以調節人和動物不同大腦區域的神經活動。但是，超聲刺激調控缺血性大腦的神經活動及促進神經康復的作用及機制尚不清楚。在本研究中，我們探討了tFUS對神經康復的影響及其潛在機制。我們製作了成年雄性ICR小鼠（n = 42）短暫大腦中動脈梗死模型。缺血後一周，連續7天（每天10分鐘）應用低頻（0.5 MHz）tFUS刺激小鼠缺血半球。於缺血14天時，進行腦梗死體積評估、神經行為學測試、小膠質細胞活化、IL-10和IL-10R水平測定。研究發現，與未進行超聲治療的卒中小鼠相比，tFUS治療小鼠的腦梗死體積顯著減少（p <0.05）。同樣，tFUS治療組小鼠的神經系統損傷嚴重程度、懸空旋轉和轉角試驗均得到改善（p <0.05）。進一步研究發現tFUS導致缺血腦區M2小膠質細胞增加， IL-10R和IL-10表達顯著上調（p <0.05）。結論：tFUS可通過促進小膠質細胞極化並進一步調節IL-10信號通路，促進腦缺血後神經修復。