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: 9294641
• 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 2021-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9294641
• 关键词: Anatomy; Area; Assessment tool; Attenuated; Autonomic Dysfunction; Autonomic nervous system; Award; Biological Preservation; Blood flow; Body Regions; Botulinum Toxins; 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; 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; Sweat; Sweating; Techniques; Temperature; Testing; Toxin; Training; Vasoconstrictor Agents; Vasodilation; Vasodilator Agents; Vasomotor; Veterans; base; body map; career; cholinergic; clinically relevant; experience; health administration; improved; innovation; insight; intradermal injection; motor impairment; nerve supply; neuroregulation; noradrenergic; novel; physical conditioning; 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已得到充分研究，并根据国际标准进行分类 标准化评估工具。同时，SCI后的自主神经损伤，尚无标准化的临床表现。 评估工具/检查，治疗具有挑战性，并且比瘫痪对生活质量造成更大的损害 1,2 SCI 后自主神经损伤的后遗症之一是热调节失调。人们普遍认为，人们 脊髓损伤患者由于体温调节功能受损，调节核心温度的能力受损 血管舒缩和催汗活动。3 在热应激的情况下，皮肤血管舒张受损会导致皮肤 血流量 (SkBF) 增加并防止对流冷却，同时削弱出汗反应 (SR) 防止蒸发冷却。因此，脊髓损伤患者难以维持热稳态， 尤其是在热应激下。迄今为止进行的身体冷却干预试验都被证明是最低限度的 成功可能是由于对 SCI 后自主神经变化缺乏清晰的机制理解。在非 SCI 中 人，介导 SkBF 和 SR 传出控制的交感胆碱能机制是 通常认为涉及一组同一组神经；然而，缺乏明确的证据。的确， 胆碱能血管舒张神经和胆碱能催汗神经实际上在解剖学上是分开的。 有趣的是，据报道，在热应激期间，患有完全脊髓损伤的人的皮肤区域 SkBF 增加但不伴随 SR 增加，其他区域 SR 增加但不伴随 SkBF 增加。7,8 这些结果表明传出胆碱能交感血管舒缩神经和传出神经 胆碱能交感催汗神经是独立的，而不是同一个。能够学习 胆碱能血管舒张神经和胆碱能催汗神经在 SCI 中的分离将为 非 SCI 和 SCI 人群的体温调节生理学研究模型，并指导后续步骤 1) 开发有效的降温技术，以尽量减少运动过程中与热有关的疾病 心脏代谢疾病患病率较高的 SCI 人群以及 2) 更定量的评估 SCI 后的体温调节和自主功能，以确定最有可能发生其后遗症的人。 目标 - 定义和测试催汗和血管舒缩活动的神经控制机制 SCI 后确定他们的传出胆碱能控制是否是通过一组解剖学上独立的神经进行的。 (1) 绘制 SCI 患者热应激期间血管舒缩和催汗活动的区域图并进行比较 温度调节损伤水平 (TLOI) 与感觉运动 LOI。 (2)测试去甲肾上腺素能是否增加 在显示 SR 增加但 SkBF 无增加的区域中，血管收缩活性减弱 SkBF 增加 在全身热应激期间。 (3)检验胆碱能突触前神经活动影响的假设 全身 SR 和 SkBF 不一致的区域的血管舒缩和/或催汗反应​​增加 热应激。方法 - 50 名慢性 SCI 患者和 25 名 AB 患者将接受被动热应激和 将概述催汗和血管舒缩活动的区域。使用溴铵离子电渗疗法进行药理学测试 和肉毒杆菌毒素皮内注射将用于操纵具有一致和 不一致的血管舒缩和催汗活动，以确定每个区域的神经控制机制。 将完整的温度调节功能区域与完整的感觉和运动功能区域进行比较。 近期和长期职业目标 - Trbovich 博士未来 5 年的职业目标包括 通过拟议的研究计划、结构化的研究培训来扩展她的专业知识和经验 该领域经验丰富的研究人员和临床医生的技能和指导。这个机会可以让她 培养必要的技能，以便将来竞争 VA 优异奖。她的长期目标是 成为退伍军人管理局医师科学家，拥有独立资助的研究项目，这将使她能够 SCI 后自主神经功能障碍领域目前尚未解答的问题有很大贡献。