Origins of Increased Motoneuron Excitability in Hemispheric Stroke

 描述(申请人提供)：痉挛是半球卒中的常见并发症，影响40%或更多的卒中幸存者。其最明显的临床特征是肌肉高张力，即肢体对外部运动的抵抗力增强。如果不治疗，这一点 音调的增加会阻碍关节运动，限制自主运动的恢复。此外，痉挛可能会导致持续性肌肉缩短，导致关节畸形，并导致肌肉痉挛。病理生理学似乎依赖于拉伸反射反应的增强，但我们不知道这种增强起源于哪里。因此，这项建议试图通过检验几种关于基本潜在机制的替代假说来探索痉挛性高张的生理起源。首先，可能有更大的兴奋性突触驱动脊髓运动神经元池，来自关键的下行脊髓通路，如前庭脊髓和/或网状脊髓束。其次，肌肉拉伸可能会在脊髓运动神经元中诱发更大和/或更长持续时间的Ia兴奋性突触电位(EPSP)。第三，运动神经元的固有膜特性可能会发生变化，如运动神经元的电压门控电导，从而产生持续的内向电流，即“PIC”。我们计划使用先进的肌电记录技术，结合新型肌腱探头(Linmot)的使用，在大脑半球中风幸存者中探索这些机制，这种探头可以在肌肉(二头肌)上施加受控的肌肉长度变化，并记录二头肌的肌力。当这些方法结合在一起时，应该允许我们区分所提出的机制的相对贡献，并应该帮助我们开发关于痉挛的生理特征的更高的诊断精度，以及设计新的治疗方法。

 DESCRIPTION (provided by applicant): Spasticity is a common complication of hemispheric stroke, impacting 40% or more of stroke survivors. Its most visible clinical feature is muscular hypertonia, or increased resistance of a limb to externally imposed motion. If left untreated, this increase in tone can impede joint motion, limiting recovery of voluntary movement. In addition, spasticity may lead to persistent muscle shortening, giving rise to joint deformity, and to muscle contracture. The pathophysiology appears to depend on an enhancement of the stretch reflex response, but we do not know where this enhancement originates. Accordingly, this proposal seeks to explore the physiological origins of spastic hypertonia by examining several alternative hypotheses about the basic underlying mechanisms. First, there could be greater excitatory synaptic drive to the spinal motoneuron pool, arising from key descending spinal pathways such as the vestibulospinal and/or reticulospinal tracts. Second, there could be larger, and/or longer-duration Ia excitatory synaptic potentials (EPSP'S) in spinal motoneurons elicited by the muscle stretch. Third, there could be changes in the intrinsic membrane properties of motoneurons such as in voltage-gated conductances of motoneurons, giving rise to persistent inward currents, or "PIC's". We plan to explore these mechanisms in hemispheric stroke survivors, using advanced EMG recording technologies, coupled with the use of a novel tendon probe (the Linmot), which imposes controlled muscle length changes on the muscle (the biceps muscle) and records biceps muscle force. These approaches, when combined, should allow us to separate the relative contributions of the proposed mechanisms, and should help us to develop greater diagnostic precision about the physiological characteristics of spasticity, as well as to design novel therapeutic approaches.