Persisting functional CNS changes following peripheral nerve repair

周围神经修复后中枢神经系统功能持续变化

• 批准号: 9198176
• 负责人: Quinn H Hogan
• 金额: --
• 依托单位: CLEMENT J. ZABLOCKI VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-01-01 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9198176
• 关键词: Adult; Afferent Neurons; Anatomy; Anesthetics; Animals; Area; Attention; Behavioral; Body Regions; Brain; Central Nervous System Diseases; Clinical; Cognitive; Communication; Communication impairment; Data; Deafferentation procedure; Disease; Electric Stimulation; Electrophysiology (science); Elements; Esthesia; Event; Excision; Face; Foundations; Functional Magnetic Resonance Imaging; Funding; Future; Goals; Imaging Techniques; Implanted Electrodes; Injury; Learning; Lesion; Light; Limb structure; Magnetic Resonance Imaging; Maps; Measures; Modality; Monitor; Motor; Nerve; Nerve Crush; Neurons; Operative Surgical Procedures; Outcome; Pathway interactions; Patients; Pattern; Performance; Peripheral; Peripheral Nerves; Peripheral nerve injury; Phase; Photosensitivity; Population; Process; Rattus; Recovery; Rehabilitation Outcome; Rehabilitation therapy; Research; Rest; Sensory; Severities; Signal Transduction; Site; Source; Stimulus; Techniques; Technology; Testing; Therapeutic; Time; Veterans; Visual; Work; design; dexterity; disability; experimental study; healing; high risk; imaging biomarker; imaging modality; improved; injured; injury and repair; longitudinal design; nerve injury; nerve transection; novel; novel therapeutic intervention; operation; optogenetics; peripheral nerve transection; prevent; public health relevance; repaired; response; sensory cortex; sensory input; sensory system; success; viral gene delivery

 DESCRIPTION (provided by applicant): Peripheral nerve injury is a frequent source of disability and a particular challenge for rehabilitation in the Veteran population. Although techniques for surgical repair have progressed, outcomes remain unpredictable. In the past, connections of the periphery to the brain had been thought to be fixed in adults, but there is a growing recognition of plasticity in brain function associated with removal of peripheral sensory input. For instance, it is known that sensory cortex associated with denervated body regions become reassigned, and disordered cortical function persists after repair of a surgical lesion. However, successful use of the limbs requires not just brain connections to peripheral targets, but also the coordinated participation o numerous activities within the brain, including interaction with other sensory sites as well as motor, visual, and cognitive areas. We therefore hypothesize that disruption of interactive brain activity underlies rehabilitation challenges after nerve injury repair. New noninvasive technology now exists to assess the integrated performance of the brain. Specifically, functional magnetic resonance imaging (fMRI) can indicate coordinated activation of various brain loci, while resting state functional connectivity MRI (rs-fMRI) reveals patterns of communication between brain sites in the absence of stimuli. Our preliminary data show substantial disruption of coordinated brain function following experimental nerve injury and repair. We have the long-term goals of defining this phenomenon in temporal and anatomic detail, which would lay the groundwork for developing an imaging biomarker that could guide personalized rehabilitation that targets appropriate specific functions. We have the additional goal of testing whether artificially maintaining afferent sensory neuron activity to the brain during the healing phase after repair may lessen or prevent brain disorganization. In the work proposed in this SPiRE application, we will obtain initial observations to substantiate our hypotheses by defining brain responses to nerve injury/repair with and without supplying replacement afferent activity, in a limited number of animals in a longitudinal fashion, using our novel techniques. Further, we will develop the means to achieve neuronal stimulation for treatment of untethered animals using implantable optogenetic light sources that activate photosensitive channels expressed in sensory neurons after viral gene delivery. We believe that extending the rehabilitation perspective beyond the nerve repair to include brain function may open the door to a new level of refined rehabilitation assessment, planning, and success.

 描述（由申请人提供）： 外周神经损伤通常是残疾的根源，也是退伍军人人口康复的特殊挑战。尽管进行手术修复技术已经取得进展，但结果仍然是不可预测的。过去，人们认为外围与大脑的连接是在成年人中固定的，但是人们对脑功能的可塑性越来越多，与去除外周的感觉输入有关。例如，众所周知，与未经根化的身体区域相关的感觉皮层被重新分配，并且在修复手术病变后的皮质功能均匀。但是，成功使用四肢不仅需要与外围目标的大脑连接，还需要大脑中的许多活动，包括与其他感觉部位以及运动，视觉和认知区域的相互作用。因此，我们假设互动脑活动的破坏是神经损伤修复后康复挑战的基础。现在存在新的无创技术来评估大脑的综合性能。具体而言，功能性磁共振成像（fMRI）可以表明各种大脑位置的协调激活，而静止状态功能连通性MRI（RS-FMRI）揭示了在没有刺激的情况下，脑部位点之间的通信模式。我们的初步数据表明，在实验性神经损伤和修复后，大脑功能严重破坏。我们的长期目标是通过临时和解剖细节来定义这一现象，这将为开发成像生物标志物的基础，该标志物可以指导针对适当特定功能的个性化康复。我们有一个附加的目标是测试在修复后的愈合阶段，是否可以人为地维持传入的感觉神经元活动可能会减少或防止脑部混乱。在此尖峰应用中提出的工作中，我们将通过使用我们的新技术以有限的纵向方式来确定脑部对神经损伤/修复的反应，或者在不提供有限数量的动物的情况下，通过定义对神经损伤/修复的脑反应，以证实我们的假设。此外，我们将使用可植入的光遗传光源来治疗无束缚动物的神经元刺激的含义，这些光源激活病毒基因递送后在感觉神经元中表达的光敏通道。我们认为，将康复的观点扩展到神经修复之外，以包括大脑功能，可能为新的精制康复评估，计划和成功打开了大门。