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Spinal Neuromodulation to Promote Physiologic and Molecular Plasticity in theInjured Spinal Cord

脊髓神经调节促进受损脊髓的生理和分子可塑性

基本信息

批准号：
10805726
负责人：
Philip J Horner
金额：
$ 46.94万
依托单位：
METHODIST HOSPITAL RESEARCH INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-20 至 2028-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10805726
关键词：
Acute Anatomy Animal Experiments Animals Area Biology Cervical Cervical spinal cord injury Cervical spinal cord structure Chronic Clinical Clinical Data Clinical Research Contusions Data Devices Dorsal Dose Effectiveness Electric Stimulation Electrodes Engineering Family Fiber Forelimb Future Gene Expression Genetic Transcription Hour Informatics Injury Investigation Lesion Locomotion Maps Methods Modeling Molecular Motor Muscle Neuronal Plasticity Paralysed Pathway interactions Patients Pattern Performance Persons Physiological Physiology Positioning Attribute Publishing Quadriplegia Quality of life Rattus Recovery Recovery of Function Rehabilitation therapy Reporting Research Retinal blind spot Rodent Role Sensory Site Speed Spinal Spinal Cord Spinal cord injury Stroke Surface Testing Time Training Traumatic Brain Injury Upper Extremity Vertebral column Walking Work candidate identification central pattern generator clinically relevant cost experience experimental study functional improvement functional plasticity gene regulatory network hand rehabilitation improved innovation insight interest intraspinal microstimulation motor recovery nerve injury neural neuroinflammation neuroregulation novel novel strategies pre-clinical restoration transcriptomics

项目摘要

Abstract There is growing interest in the use of electrical stimulation to promote the recovery of sensorimotor and autonomic function after neural injury. Previous research from our lab and others has demonstrated that stimulation of spinal lumbar segments activates central pattern generators, which, in turn, facilitates standing and walking. However, while there is extensive animal, pre-clinical, and clinical data examining the impact of lumbar stimulation, studies that apply neuromodulation to the cervical spinal cord for upper limb are very limited. Here, we propose that fundamental blind spots exist in the field of neuromodulation for upper limb, including where to stimulate anatomically, how to dose and, especially, mechanisms of action. The Horner lab has developed a clinically relevant rat model of cervical spinal cord injury and engineered a self-contained epidural stimulation device that can be deployed in freely behaving rats to stimulate sensorimotor circuitry from multiple surfaces of the spinal cord. Hence, we are well positioned to test critically important hypotheses on the role of cervical stimulation in the restoration of upper limb function. We present exciting preliminary data demonstrating that epidural stimulation of the cervical spinal cord improves forelimb function. The rationale for the proposed research is that the site of epidural stimulation provides unique access to motor circuitry. We hypothesize that ventral positioning of electrodes (VSS) will provide access to stimulate motor circuitry at the site of lesion that are inaccessible from the more common dorsal approach (DSS). Further, we propose that VSS will produce novel mechanisms of function plasticity that can amplify recovery when combined with DSS. To test this hypothesis, we propose the following aims: Aim 1: Determine acute molecular and physiological mechanisms of VSS when applied to subacute cervical spinal cord injury. Aim 2: Establish the functional impact of site of stimulation and rehabilitative training on recovery from early chronic cervical spinal cord injury. Aim 3: Establish the synergistic effects of combined VSS and DSS after cervical spinal cord injury. These studies will explore an exciting new approach to promote neural recovery of the upper limb, an area of research that has had limited investigation, but remains a primary concern for the patient. Our approach will rigorously establish the physiological and functional effects of the site of stimulation on the molecular and physiological mechanisms of upper limb plasticity.

摘要