Vasomotor and Sudomotor Activity During Heat Stress in Spinal Cord Injury

脊髓损伤热应激期间的血管舒缩和催汗活动

• 批准号: 10058778
• 负责人: Michelle Trbovich
• 金额: --
• 依托单位: SOUTH TEXAS VETERANS HEALTH CARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-01-01 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10058778
• 关键词: Anatomy; Area; Assessment tool; Attenuated; Autonomic Dysfunction; Autonomic nervous system; Award; Blood flow; Body Regions; Botulinum Toxins; Cardiometabolic Disease; Cause of Death; Chronic; Clinical Assessment Tool; Clinical assessments; Complex; Convection; Cutaneous; Development; Diabetes Mellitus; Disease; Efferent Neurons; Exercise; Funding; Future; Goals; Health; Heart Diseases; Heat Stress Disorders; High Prevalence; Homeostasis; Humidity; Imagery; Impairment; Individual; Injury; International; Intervention; Intervention Trial; Iodine; Iontophoresis; Laser-Doppler Flowmetry; Lasers; Lesion; Maps; Measures; Mediating; Mentorship; Mission; Modeling; Monitor; Motor; Nerve; Neurologic; Neurotransmitters; Obesity; Paralysed; Pathway interactions; Peripheral; Personal Satisfaction; Persons; Pharmacology; Physicians; Physiological; Physiology; Population; Quality of life; Reporting; Research; Research Personnel; Research Technics; Risk; Scientist; Sensorimotor functions; Sensory; Skin; Spinal cord injury; Standardization; Starch; Structure; Sweating; Techniques; Temperature; Testing; Toxin; Training; Vasoconstrictor Agents; Vasodilation; Vasodilator Agents; Vasomotor; Veterans Health Administration; base; body map; career; cholinergic; clinically relevant; experience; improved; innovation; insight; intradermal injection; motor impairment; nerve supply; neuroregulation; noradrenergic; novel; physical conditioning; preservation; presynaptic; presynaptic neurons; prevent; programs; response; skills

Sensory and motor impairment after spinal cord injury (SCI) is well studied and classified with international standardized assessment tools. Meanwhile, autonomic impairment after SCI, is without a standardized clinical assessment tool/exam, is challenging to treat and causes greater impairment in quality of life than paralysis alone.1,2 One sequela of autonomic injury post SCI is thermal dysregulation. It is well accepted that persons with spinal cord injury have impaired ability to regulate core temperature due to compromised thermoregulatory vasomotor and sudomotor activity.3 In the setting of heat stress, impaired cutaneous vasodilation obviates skin blood flow (SkBF) increases and prevents convective cooling while impaired sweating responses (SR) prevents evaporative cooling. As a result, persons with SCI have difficulty maintaining thermal homeostasis, especially under heat stress. Body cooling intervention trials performed to date have all proven minimally successful likely due to lack of clear mechanistic understanding of autonomic change post-SCI. In non-SCI persons, sympathetic cholinergic mechanisms that mediate efferent control of both SkBF and SR are commonly thought to involve one and the same set of nerves; however, definitive proof is lacking. Indeed, cholinergic vasodilator nerves and cholinergic sudomotor nerves could actually be anatomically separate. Interestingly, it has been reported that during heat stress, persons with complete SCI have skin regions where SkBF increases without concomitant SR increases and other regions where SR increases without concomitant SkBF increases.7,8 These results suggest that efferent cholinergic sympathetic vasomotor nerves and efferent cholinergic sympathetic sudomotor nerves are separate, rather one and the same. Being able to study cholinergic vasodilator nerves and cholinergic sudomotor nerves in isolation in SCI will provide a valuable model for thermoregulatory physiology studies in non-SCI and SCI persons, and guide next steps in development of 1) An effective cooling technique so as to minimize heat related illness during exercise in the SCI population with a high prevalence of cardiometabolic disease and 2) A more quantitative assessement of thermoregulatory and autonomic function post-SCI to determine persons at greatest risk of its sequela. OBJECTIVES - To define and test the neurological control mechanisms of sudomotor and vasomotor activity after SCI to determine if their efferent cholinergic control is through an anatomically separate set of nerves. (1) Map areas of vasomotor and sudomotor activity during heat stress in persons with SCI and compare thermoregulatory level of injury (TLOI) with sensorimotor LOI. (2) Test whether increased noradrenergic vasoconstrictor activity attenuates SkBF increases in regions that show SR increases but no SkBF increases during whole body heat stress. (3) Test the hypothesis that cholinergic presynaptic nerve activity effects vasomotor and/or sudomotor responses in regions with discordant SR and SkBF increases during whole body heat stress. METHODS - 50 persons with chronic SCI and 25 AB persons will undergo passive heat stress and areas of sudomotor and vasomotor activity will be outlined. Pharmacologic tests using bretylium iontophoresis and onabotulinum toxin intradermal injections will be utilized to manipulate areas with concordant and discordant vasomotor and sudomotor activity to determine the neurological control mechanisms in each area. Areas of intact thermoregulatory function will be compared to areas of intact sensory and motor function. IMMEDIATE AND LONG TERM CAREER GOALS - Dr. Trbovich's career goals over the next 5 years include expanding her expertise and experience through the proposed research plan, structured training in research skills and mentorship under experienced researchers and clinicians in the field. This opportunity will allow her to develop necessary skills to compete for a VA Merit Review Award in the future. Her long-term goal is to become a VA physician scientist with an independently funded research program that will allow her to significantly contribute to current unanswered questions in the field of autonomic dysfunction after SCI.

脊髓损伤（SCI）后的感觉和运动障碍对国际进行了良好的研究和分类 标准化评估工具。同时，SCI后的自主性障碍没有标准化的临床 评估工具/考试，对治疗和造成比瘫痪质量更大的治疗和造成更大的损害的挑战 1,2 SCI后自主损伤的续集是热失调。人们很公认的人 脊髓损伤因受损调节而导致调节核心温度的能力受损 血管舒张症和促成运动活性。3在热应力的情况下，皮肤血管舒张受损可避免皮肤 血流（SKBF）增加并防止对流冷却，而出汗反应受损（SR） 防止蒸发冷却。结果，SCI患者难以维持热稳态， 特别是在热应力下。迄今为止进行的身体冷却干预试验已被证明很少 成功的可能是由于SCI后对自主变化缺乏清晰的机械理解。在非SCI中 介导SKBF和SR的传出控制的人，同情胆碱能机制是 通常被认为涉及一组神经；但是，缺乏确定的证据。的确， 胆碱能血管扩张剂神经和胆碱能神经神经实际上可能是解剖学分开的。 有趣的是，据报道，在热压力期间，具有完整SCI的人有皮肤区域 SKBF增加而没有伴随的SR增加，而其他区域则增加了SR而不同时增加 SKBF增加。7,8这些结果表明，传出的胆碱能交感神经和传出 胆碱能交感神经神经是分开的，而是相同的。能够学习 胆碱能血管扩张剂神经和胆碱能的SCI中的胆碱能神经将提供有价值的 非SCI和SCI人的热调节生理研究模型，并指导下一步 开发1）一种有效的冷却技术，以最大程度地减少与热有关的疾病 心脏代谢疾病患病率很高的SCI人群和2）对 SCI之后的温度调节和自主功能，以确定其后遗症风险最大的人。 目的 - 定义和测试Sudomotor和血管舒缩活性的神经系统控制机制 在SCI之后，确定其发出的胆碱能控制是否是通过解剖上分开的神经组成的。 （1） SCI患者的热应激期间血管舒张舒马运动和促成活动的地图区域并进行比较 用感觉运动LOI的损伤温度损伤水平。 （2）测试是否增加了甲肾上腺素能 血管收缩活动可减弱显示SR增加但没有SKBF增加的区域的SKBF增加 在全身热应激期间。 （3）检验胆碱能突触前神经活性作用的假设 全身不一致的SR和SKBF区域中的血管舒张症和/或Sudomotor响应增加 热应力。方法-50人患有慢性SCI和25人 将概述Sudomotor和血管舒缩活性区域。使用甲酸离子疗法的药理测试 并将利用果核毒素毒素内注射剂 不一致的血管舒张症和促成活性，以确定每个区域中的神经系统控制机制。 完整的温度调节功能区域将与完整的感觉和运动功能区域进行比较。 直接和长期职业目标 - Trbovich博士在接下来的5年中的职业目标包括 通过拟议的研究计划扩大她的专业知识和经验，研究的结构化培训 该领域经验丰富的研究人员和临床医生的技能和指导。这个机会将使她 发展必要的技能，以争夺未来的VA功绩审查奖。她的长期目标是 成为一名拥有独立资助的研究计划的VA医师科学家，这将使她能够 在SCI后，在自主神经功能障碍领域的当前未解决问题。