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.

项目摘要/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。不幸的是，临床前研究和临床上可用的治疗方法都没有足够的 解决这些神经活动变化之间的复杂相互关系，尽管人们普遍认识到 重叠的脊椎网络中不适当的神经传输是它们的基础。这种机械论 重叠表明，这两种旨在促进一个领域康复的疗法可能会影响多个领域 域同时存在，并且有可能利用脊髓网络的密集互连 有目的地设计多种模式的康复治疗--即，那些专门旨在解决更多 而不是SCI的一个后果。这项工作的最终目标是提高生活在一起的人的生活质量 通过开发基于对脊柱的综合神经力学理解的多模式疗法来治疗脊髓损伤 脐带功能。目标1(F99阶段)将专注于神经技术驱动的多模式治疗，以同时 在临床相关的脊髓损伤大鼠模型中，增加自主运动输出，同时改善神经病理性疼痛。至 为此，我将研究脊髓灰质运动占优势区域的神经元对 脊髓伤害性感觉过程，传统上只在感官上进行研究和表征- 脊髓灰质的优势区域。我们将测试潜在的疼痛处理网络是否存在于 脊髓灰质的运动优势区域，在伤害性时期变得不受掩蔽 脊髓损伤大鼠的传播。我们预测，这个以前未被发现的网络的出现将是 在与脊髓损伤相关的神经病理性疼痛的大鼠中越来越明显。如果确定，这个网络可能会提供一个新的 神经假体治疗的目标是提供多模式康复益处。这将解决两个关键问题 脊髓损伤人群未得到满足的需求：脊髓损伤相关神经性疼痛和多模式的非阿片类药物治疗 康复。目标2(K00阶段)将侧重于加强多模式康复，旨在同时 改善脊髓损伤后的膀胱、肠道和性功能障碍(即盆底功能障碍)。功能的恢复 因盆底肌肉神经控制不当而受损是人们生活在康复领域的首要任务 和SCI一起。然而，尽管对身心健康有影响，但盆底肌肉的神经控制 是脊椎生理学和神经康复研究相对较少的领域。因此，在K00阶段I将 通过躯体神经和自主神经的整合来研究盆底肌肉的脊神经控制， 这对维持适当的盆底功能是必不可少的，而且几乎每一次脊髓损伤都会破坏这种功能。我 然后准备建立一条独立的研究路线，开发多种模式的疗法，以解决 患有脊髓损伤相关的肠、膀胱和性功能障碍的患者所面临的交叉挑战。