运动神经元活化及感觉-运动传导环路易化在面肌痉挛中的作用研究

Idiopathic hemifacial spasm (HFS) is due to abnormal facial nerve discharge caused by cerebrovascular compression. The nerve that dominates facial muscles originates from the facial nucleus; However, it is unclear whether and how vascular compression affects the motoneurons in the facial nucleus (facial motonueron, FMN). Studies have found that the mechanoreceptor TRPV4 played a crucial role in the sensory neuronal activation and trigeminal hyperalgesia caused by cerebrovascular compression of trigeminal nerve. We assume that as for HFS, which shares a similar cause with trigeminal neuralgia, vascular compression may also increase the excitability of FMN through activation of TRPV4, and may further affect the communication between FMNs (synaptic plasticity). Nerve conduction examination showed that in HFS patients, the affected side facial nerve discharge enhanced when stimulating the trigeminal nerve. Given the possibility of synaptic remodeling in FMN, we presume that the synaptic transmission from trigeminal sensory afferent to facial motor efferent is facilitated. Moreover, HFS is usually triggered or aggravated by emotional stress, which indicates that emotional stress related centers might also be involved in regulating the discharge pattern of FMN. This project intends to prove the above hypothesis through establishing HFS animal model and application of immunofluorescence, western blot, immunoelectron microscopy and patch-clamp techniques. This project is of great significance in exploring the pathogenesis of HFS and finding neuromodulation methods for the treatment of HFS.

特发性面肌痉挛（HFS）是由血管压迫面神经引起神经异常放电所致。支配面肌运动的神经起源于面神经核，但HFS时血管压迫对面神经核运动神经元（FMN）会产生怎样的影响及如何产生影响，目前并不清楚。研究发现，感受机械性刺激的TRPV4在血管压迫三叉神经引起神经元活化、痛觉过敏的发生中至关重要。因此，HFS时，血管压迫可能也会通过激活TRPV4提高FMN的兴奋性，并进一步影响FMN间信息传递的方式。神经传导检测提示，刺激HFS患者三叉神经，患侧面神经放电增强，结合FMN可能发生的活化，我们推测，HFS时可能还存在面部感觉-运动传导环路突触传递的易化。情绪紧张能诱发或加重HFS，因此，情绪应激相关中枢可能也参与了FMN的调节。本研究拟构建HFS动物模型，应用免疫荧光、免疫组化、电镜、膜片钳等技术对上述假设予以证明，这对深入认识HFS的发病机制以及从神经调控方面寻求不开颅治疗HFS的方法具有重要意义。

特发性面肌痉挛（HFS）是由血管压迫面神经引起神经异常放电所致，情绪紧张能诱发或加重HFS。但机械压迫以及情绪应激如何影响面神经的兴奋性目前并不清楚。本研究通过建立HFS动物模型，应用免疫荧光、Western blot 和膜片钳等方法，观察到HFS模型动物面神经核运动神经元（FMN）内c-fos、ERK表达增高，FMN静息膜电位升高，提示HFS时FMN兴奋性增强；此外，HFS模型组突触传递相关的受体（NA2A/GluA1）和蛋白（Synapsin）表达升高，FMN的基强度（Rheobase）降低，step电压诱发的动作电位数目显著增高，提示HFS时FMN的可兴奋性增强。激活机械敏感性受体通道（TRPV4）能够使FMN去极化，动作电位发放频率增加。应激相关激素TRH、CRH 和NE均能够显著增加FMN自发的兴奋性突触后电流（sEPSCs）的频率和幅度，提示情绪应激可能能够通过兴奋FMN诱发或加重HFS。上述结果对我们认识HFS的发病机制和情绪应激对HFS的影响方式具有重要意义。我们在临床工作中发现，HFS发病初期，患侧瞬目反射波幅增高，提示存在三叉-面神经（感觉-运动）传导通路的易化。椎动脉是造成压迫的血管中最为粗大的，椎动脉的解剖和走形变异与HFS发病侧别具有相关性。通过植入物对面神经进行彻底解压同时避免接触面神经出脑干段能够有效改善HFS的手术预后。