Integrative spinal physiology to restore neural control of sensorimotor functions after neurological injury

综合脊柱生理学恢复神经损伤后感觉运动功能的神经控制

• 批准号: 10829116
• 负责人: Maria Fernanda Bandres
• 金额: $ 3.54万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-15 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10829116
• 关键词: Address; Anesthesia procedures; Animals; Area; Autonomic Dysfunction; Behavior; Bladder; Bladder Dysfunction; Blood Pressure; Characteristics; Chest; Clinical; Combined Modality Therapy; Communication; Complex; Development; Doctor of Philosophy; Electric Stimulation; Engineering; Frequencies; Goals; Health; Heart Rate; Horns; Impairment; Implant; Individual; Injury; Intestines; Maintenance; Measures; Mental Health; Microelectrodes; Modeling; Motor; Motor Neurons; Motor output; Movement; Nervous System Trauma; Neurons; Nociception; Noise; Pain; Paralysed; Pattern; Pelvic Floor Muscle; Pelvic floor dysfunction; Pelvic floor structure; Persons; Phase; Physiology; Population; Postdoctoral Fellow; Process; Public Health; Quality of life; Rattus; Readiness; Recovery; Reflex action; Rehabilitation therapy; Research; Respiration; Sensorimotor functions; Sensory; Sex Functioning; Sexual Dysfunction; Spinal; Spinal Cord; Spinal cord injury; Synaptic Transmission; Technical Expertise; Testing; Unconscious State; Vertebral column; Work; clinically relevant; comparative; design; dorsal horn; efficacious treatment; gray matter; improved; in vivo; innovation; interest; lens; motor deficit; motor impairment; multimodality; neural; neural patterning; neurological rehabilitation; neuroprosthesis; neuroregulation; neurotechnology; non-opioid analgesic; pain processing; painful neuropathy; physical conditioning; pre-clinical research; primary outcome; programs; psychologic; restoration; sensory feedback; spatiotemporal; transmission process

Project Summary/Abstract Spinal cord injury (SCI) often results in reduced voluntary motor output, neuropathic pain, and autonomic dysfunction. Unfortunately, pre-clinical research and clinically available therapies alike have failed to adequately address the complex interrelationships amongst these changes in neural activity, despite widespread recognition that inappropriate neural transmission in overlapping spinal networks underpins them all. This mechanistic overlap suggests both that therapies intended to enhance recovery in one domain will likely impact multiple domains simultaneously and that it may be possible to leverage the dense interconnectivity of spinal networks to purposefully engineer multi-modal rehabilitation therapies – i.e., those specifically intended to address more than one consequence of SCI. The ultimate goal of this work is to enhance quality of life for people living with SCI by developing multi-modal therapies grounded in an integrative, neuro-mechanistic understanding of spinal cord function. Aim 1 (F99 Phase) will focus on neurotechnology-driven multi-modal therapies to simultaneously increase voluntary motor output while ameliorating neuropathic pain in a clinically relevant rat model of SCI. To do so, I will study potential contributions of neurons in the motor-dominant regions of the spinal gray matter to the spinal nociceptive process overall, which is traditionally only studied and characterized in the sensory- dominant regions of the spinal gray matter. We will test whether a latent pain-processing network is present in motor-dominant regions of the spinal gray matter, which becomes unmasked during periods of nociceptive transmission in rats with SCI. We predict that the emergence of this previously undetected network will be increasingly evident in rats with SCI-related neuropathic pain. If identified, this network could provide a new target for neuroprosthetic therapies to deliver multimodal rehabilitation benefits. This would address two critical unmet needs of the SCI population: non-opioid treatments for SCI-related neuropathic pain and multimodal rehabilitation. Aim 2 (K00 Phase) will focus on enhancing multi-modal rehabilitation intended to simultaneously improve bladder, bowel, and sexual dysfunction after SCI (i.e., pelvic floor dysfunction). Restoration of functions compromised by inappropriate neural control of pelvic floor muscles is a top rehabilitation priority for people living with SCI. Yet, despite its impact on physical and psychological health, the neural control of pelvic floor muscles is a comparatively understudied area of spinal physiology and neurorehabilitation. Thus, in the K00 Phase I will study the spinal neural control of pelvic floor muscles through the lends of somatic and autonomic integration, which is both essential for maintaining appropriate pelvic floor function and is disrupted by nearly every SCI. I will then be prepared to establish an independent research line developing multi-modal therapies that address the intersectional challenges faced by people living with SCI-related bowel, bladder, and sexual dysfunction.

项目总结/摘要 脊髓损伤（SCI）通常导致自主运动输出减少、神经性疼痛和自主神经功能障碍。 功能障碍不幸的是，临床前研究和临床可用的治疗方法都未能充分 解决神经活动中这些变化之间复杂的相互关系，尽管广泛认识到 重叠的脊髓网络中不适当的神经传输是它们的基础。这种机械 重叠表明，旨在促进一个领域恢复的治疗可能会影响多个领域， 同时，它可以利用脊椎网络的密集互连性， 有目的地设计多模式康复疗法-即，那些特别旨在解决更多 SCI的后果之一。这项工作的最终目标是提高生活质量的人与 通过开发基于对脊髓损伤的综合性神经机制理解的多模式疗法， cord功能目标1（F99阶段）将重点关注神经技术驱动的多模式治疗， 在临床相关SCI大鼠模型中增加自主运动输出同时改善神经性疼痛。到 这样做，我将研究脊髓灰质运动主导区神经元的潜在贡献， 脊髓伤害性过程的整体，这是传统上只研究和表征的感觉， 脊髓灰质的优势区域。我们将测试是否存在一个潜在的疼痛处理网络， 脊髓灰质的运动主导区域，在伤害性感受期间变得暴露 在SCI大鼠中的传播。我们预测，这种以前未被发现的网络的出现将是 在SCI相关神经性疼痛大鼠中越来越明显。如果被发现，这个网络可以提供一个新的 神经修复治疗的目标，以提供多模式康复的好处。这将解决两个关键问题 SCI人群未满足的需求：SCI相关神经性疼痛的非阿片类药物治疗和多模式 康复活动.目标2（K 00阶段）将侧重于加强多模式康复， 改善SCI后的膀胱、肠和性功能障碍（即，骨盆底功能障碍）。恢复职能 由于骨盆底肌肉的神经控制不当而受到损害，这是生活在美国的人们的首要康复任务。 关于SCI然而，尽管它对身体和心理健康的影响，骨盆底肌肉的神经控制， 是脊柱生理学和神经康复的一个相对研究不足的领域。因此，在K 00阶段I中， 通过躯体和自主神经的整合来研究骨盆底肌肉的脊髓神经控制， 这对于维持适当的骨盆底功能是必不可少的，并且几乎被每一个SCI破坏。我 然后将准备建立一个独立的研究线，开发多模式疗法， SCI相关的肠道、膀胱和性功能障碍患者所面临的交叉挑战。