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.

项目概要/摘要 脊髓损伤 (SCI) 通常会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疗法都未能充分 尽管已得到广泛认可，但仍需解决这些神经活动变化之间复杂的相互关系 重叠脊柱网络中不适当的神经传递是所有这些的基础。这种机制 重叠表明旨在促进某一领域恢复的疗法可能会影响多个领域 同时域，并且有可能利用脊柱网络的密集互连性 有目的地设计多模式康复疗法——即那些专门旨在解决更多问题的疗法 比 SCI 的后果之一。这项工作的最终目标是提高患有这种疾病的人们的生活质量 通过开发基于对脊柱的综合、神经机制理解的多模式疗法来治疗 SCI 绳功能。目标 1（F99 阶段）将重点关注神经技术驱动的多模式疗法，同时 在临床相关的 SCI 大鼠模型中增加随意运动输出，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域的神经元对 整个脊髓伤害感受过程，传统上仅在感觉方面进行研究和表征 脊髓灰质的主要区域。我们将测试潜在的疼痛处理网络是否存在 脊髓灰质的运动主导区域，在伤害性感受期间会暴露出来 SCI 大鼠中的传播。我们预测这个以前未被发现的网络的出现将是 在患有 SCI 相关神经性疼痛的大鼠中越来越明显。如果确定，该网络可以提供新的 神经修复疗法的目标是提供多模式康复益处。这将解决两个关键问题 SCI 人群未满足的需求：针对 SCI 相关神经性疼痛的非阿片类药物治疗和多模式治疗 康复。目标 2（K00 阶段）将侧重于加强多模式康复，旨在同时 改善 SCI 后的膀胱、肠道和性功能障碍（即盆底功能障碍）。功能恢复 因盆底肌肉神经控制不当而受到损害是人们康复的首要任务 与SCI。然而，尽管盆底肌肉的神经控制对身体和心理健康有影响， 是脊柱生理学和神经康复领域研究相对较少的领域。因此，在K00第一阶段将 通过躯体和自主神经整合研究盆底肌肉的脊髓神经控制， 这对于维持适当的盆底功能至关重要，但几乎每一次 SCI 都会破坏这一功能。我 然后将准备建立一个独立的研究线，开发解决问题的多模式疗法 患有 SCI 相关肠道、膀胱和性功能障碍的人面临的交叉挑战。