脊髓损伤（SCI）后痉挛会严重影响生活质量，运动训练可有效缓解痉挛，但机制尚未阐明。既往研究表明，SCI后GAD65/67（抑制性神经递质GABA的合成酶）合成减少，促使了痉挛的产生。我们前期研究发现，运动训练可增加BDNF/TrkB、CREB、GAD67的合成，减轻SCI后痉挛；阻断BDNF/TrkB后，上述作用则被抑制。因此，我们推测运动训练可能调控BDNF-ERK-CREB-GAD65/67途径，增加GABA合成，减轻SCI后痉挛。为证实此假说，我们在动物水平验证Ras/ERK、CREB对GAD65/67表达的影响；在细胞水平验证CREB对GAD65/67转录的调控；在临床层面探究运动强度与SCI患者血液BDNF和CREB水平及痉挛预后的相关性。本研究将阐明BDNF-ERK-CREB-GAD65/67途径在运动训练改善SCI后痉挛中的作用，为SCI运动训练方案的制定提供理论依据。

Spasticity is one of the major complications following spinal cord injury (SCI) which would possibly devastate patients’ quality of life. Although exercise rehabilitation has been proved to ameliorate spasticity, the underlying mechanisms remain unclear. Recent studies have revealed that the decrease in the synthesis of GAD65/67 (synthetase of inhibitory transmission-GABA) following SCI promotes the occurrence of spasticity. According to our previous studies, the incidence and tension of spasticity were reduced by exercise rehabilitation through enhanced level of BDNF/TrkB, CREB, and GAD67. However, the mitigation was restrained by blocking BDNF/TrkB. Hence, we presume that exercise rehabilitation might regulate the BDNF-ERK-CREB-GAD65/67 pathway, and thus promote the synthesis of GABA which in turn relieve the rate and tension of spasticity. To clarify this hypothesis, experiments will be designed to demonstrate the regulatory impact of Ras/ERK, and CREB on GAD65/67 expression in SCI rat model. In addition, the mechanism will be investigated to figure out the transcriptional regulation of CREB on GAD65/67 in vitro. Finally, clinical research will be carried out to explore the probability of the amount of BDNF and CREB in blood as indicators of prognoses of spasticity. Generally, the project aims to clarify the mechanisms of improvement in spasticity after SCI through BDNF-ERK-CREB-GAD65/67 and guide the theoretical formulation of clinical exercise rehabilitation program for SCI patients.