Targeting urinary tract dysfunctions after spinal cord injury with epidural stimulation

通过硬膜外刺激治疗脊髓损伤后的尿路功能障碍

• 批准号: 10656916
• 负责人: CHARLES H. HUBSCHER
• 金额: $ 35万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 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 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10656916
• 关键词: Acute; Address; Aftercare; Anesthesia procedures; Ataxia; Bilateral; Biological Markers; Bladder; Bladder Tissue; Cell Nucleus; Cells; Chronic; Clinical Trials; Clinical effectiveness; Commissure; Contusions; Development; Devices; Dorsal; Effectiveness; Electrodes; FOS Protein; Functional disorder; Goals; Health; Health Care Costs; Histology; Hour; Human; Immune; Individual; Location; Locomotor training; Lower urinary tract; Maintenance; Maps; Mediating; Modeling; Molecular Biology; Motor; Nerve; Neurons; Outcome; Pattern; Pelvis; Peripheral; Quality of life; Rattus; Recommendation; Reflex action; Reflex control; Rehabilitation therapy; Source; Sphincter; Spinal; Spinal Cord; Spinal Cord Tract; Spinal cord injury; Structure; Synapses; System; Technology; Training; Urethane; Urinary tract; Vertebral column; chemokine; cholinergic; clinically relevant; design; dorsal horn; electric field; experimental study; functional outcomes; gray matter; improved; multi-electrode arrays; nerve transection; neural; neurological rehabilitation; neuroregulation; novel; peripheral nerve transection; postsynaptic; pre-clinical research; preclinical study; pressure; response; response to injury; restoration; timeline; treadmill; urologic

(PLEASE KEEP IN WORD, DO NOT PDF) Abstract Spinal cord epidural stimulation (scES), which creates an electrical field directly over the spinal cord, has shown early promise for the restoration of voluntary and reflex control of the lower urinary tract (LUT) among individuals with spinal cord injuries (SCI). A major advantage of the proposed multi-electrode array over the Interstim system and transcutaneous approach is the versatility of the multi-electrode and the ability to activate multiple structures and functions simultaneously with a single electrode placement and device. The goal of this pre-clinical research is to optimize scES for functional benefits and identify mechanism(s) to better facilitate daily management and improve quality of life. It is hypothesized that effective scES for both bladder storage and emptying occurs when initiated chronically post-SCI through activation of spinal bladder circuits including neurons within the dorsal commissure, superficial dorsal horn, sacral parasympathetic nucleus, and Onuf’s nucleus, with the requirement of intact hypogastric/pelvic/pudendal nerves, and with greater effectiveness when given in combination with locomotor training. For Aim 1, previously identified optimal parameters will be used to identify neural components of the spinal networks contributing to scES-induced LUT effects with different chronicity’s post-SCI in urethane-anesthetized rats using two approaches: a) Fos protein induction (a marker for postsynaptic activation of spinal neurons), and b) select peripheral nerve transections. Examining the contributing spinal central regions activated with scES and key peripheral components for different aspects of LUT function will provide novel targets for further development and refinement of epidural arrays and controllers. For Aim 2, the impact of scES on LUT functions in SCI rats after treatment with differing periodicities of locomotor training will be examined to address the potential added benefit of a combinatory approach (neuromodulation with rehabilitation). A sub-aim examines the underlying Fos induced central neural components, as plasticity is likely induced with training. Both aims will also include bladder histology/molecular biology assessments re the effects of chronicity/training. These studies will significantly move the SCI field forward by providing optimal parameters and locations for targeting LUT function that will be key for advancing the existing technology.

（请保持言语，不要PDF） 抽象的 脊髓硬膜外模拟（SCES）直接在脊髓上产生电场，已经表现出对脊髓损伤（SCI）中尿路（LUT）自愿控制（LUT）的自愿控制和反射控制的早期承诺。所提出的多电极阵列比杂种系统和经态方法的主要优点是多电极的多功能性，以及与单个电极放置和设备相似地激活多个结构和功能的能力。这项临床前研究的目的是优化SCE的功能福利，并确定机制，以更好地促进日常管理和改善生活质量。据推测，当通过激活脊髓膀胱膀胱回路（包括背侧委员会内神经元），浅表性角，sacral核心核心核心以及与完整的核us的核能以及智力/pelvical效率的要求时，伴有脊髓膀胱膀胱回路，包括脊柱神经元在内，伴有脊柱膀胱膀胱回路，以及智力/pelvictric/perefient的核能，伴随着脑/plevic的效率，这是有效的SCE。运动训练。对于AIM 1，先前确定的最佳参数将用于识别脊柱网络的神经成分，这些脊柱网络的神经成分有助于SCES诱导的LUT效应，并使用两种方法在尿甲烷 - 动理大鼠中具有不同的慢性后SCI，使用两种方法：A）FOS蛋白诱导（用于脊柱神经元的突触后神经元的标记物）。检查LUT功能不同方面的SCE和关键外围成分激活的脊柱中央区域将为硬膜外阵列和控制器的进一步开发和完善提供新的目标。对于AIM 2，将检查SCE对SCE的影响在与运动训练的周期性周期性治疗后对SCI大鼠的LUT功能的影响，以解决组合方法的潜在额外益处（神经调节康复）。子-AIM检查基础FOS引起的中央神经成分，因为训练可能会引起可塑性。这两个目标还将包括膀胱组织学/分子生物学评估，这是慢性/训练的影响。这些研究将通过提供针对LUT功能的最佳参数和位置来大大推动SCI领域的发展，这将是推进现有技术的关键。