超声通过运动控制和BDNF-KCC2通路改善卒中后肢体痉挛的神经调控机制研究

肢体肌肉痉挛是影响脑卒中患者运动功能和致残的主要原因，痉挛的控制是神经康复的研究热点。聚焦超声对多种神经系统疾病起到治疗效果，而聚焦超声通过无创中枢神经调控改善卒中后痉挛的机制尚不清楚。脑卒中后亚急性期外源性脑源性神经营养因子（BDNF）或康复治疗产生的内源性BDNF可通过抑制钙离子通道上调运动神经元膜上钾氯联合转运蛋白2（KCC2）的表达而改善痉挛。我们前期研究发现，经颅低强度聚焦超声治疗的疗效与钙离子通道的细胞内应答高度相关，并可影响卒中后大鼠痉挛模型脊髓内BDNF的表达。由此推测聚焦超声可能通过BDNF-KCC2途径对痉挛产生影响。本课题拟采用经颅聚焦超声辐照大鼠脑出血后痉挛模型，检测相关脑区神经元及胶质细胞内BDNF、KCC2的变化，结合抑制BDNF-KCC2通路观察聚焦超声对脊髓神经元兴奋性和痉挛的影响，探索聚焦超声治疗大鼠脑出血后痉挛的作用与机制，为临床治疗痉挛提供依据。

Spasticity is the main reason that affects motor function and disability in patients with stroke. Control of spasticity is the focus and difficulty of stroke rehabilitation. Focused ultrasound is proven to produce therapeutic effects in a variety of neurological diseases. But the mechanism by which focused ultrasound improves spasm after stroke through non-invasive central nervous regulation is not clear. Exogenous brain-derived neurotrophic factor (BDNF) produced by rehabilitation therapy in the sub-acute phase after stroke can up-regulate the expression of potassium chloride and transporter 2 (KCC2) of motor neuron membranes by inhibiting calcium channels and improve spasms. Our previous study found that the effect of transcranial low-intensity focused ultrasound treatment is highly correlated with the intracellular response of calcium channels and can affect the expression of BDNF in the brain of post-stroke spasm rat models. It is speculated that focused ultrasound may have an effect on spasm through the BDNF-KCC2 pathway. This project intends to use a cranial focused ultrasound to irradiate rat cerebral hemorrhage spasm model, observe the effect of focused ultrasound on spinal neuron excitability and spasm by inhibiting BDNF-KCC2 channel, and explore focused ultrasound through BDNF-KCC2 pathway in treating rats The role and mechanism of spasm after intracerebral hemorrhage is of great significance to clarify the neural regulatory mechanism of focused ultrasound and provide ideas for the treatment of spasticity.