Vasomotor and Sudomotor Activity During Heat Stress in Spinal Cord Injury

脊髓损伤（SCI）后的感觉和运动障碍得到了很好的研究和分类， 标准化评估工具。同时，SCI后自主神经功能的损害，目前尚无规范的临床研究 评估工具/检查，治疗具有挑战性，对生活质量的损害比瘫痪更大 1，2 SCI后自主神经损伤的后遗症之一是热失调。人们普遍认为 脊髓损伤患者由于体温调节受损， 3在热应激的情况下，受损的皮肤血管舒张使皮肤 血流量（SkBF）增加，并防止对流冷却，而受损的出汗反应（SR） 防止蒸发冷却。因此，SCI患者难以维持热稳态， 特别是在热应激下。迄今为止进行的身体冷却干预试验都证明， 成功可能是由于缺乏对SCI后自主神经变化的明确机制理解。非SCI 人，交感胆碱能机制，介导传出控制的SkBF和SR是 通常认为涉及同一组神经;然而，缺乏确切的证据。的确， 胆碱能血管扩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，完全SCI患者的皮肤区域， SkBF增加而不伴随SR增加，以及SR增加而不伴随SR增加的其他区域 SkBF增加。7，8这些结果表明，传出胆碱能交感血管神经和传出 胆碱能交感催汗神经是分开的，而不是同一个。能够研究 在SCI中分离胆碱能血管扩张神经和胆碱能泌汗神经将提供有价值的 非SCI和SCI患者体温调节生理学研究的模型，并指导 1）开发有效的冷却技术，以最大限度地减少运动期间与热有关的疾病， 心脏代谢疾病患病率高的SCI人群和2）更定量的评估 SCI后的体温调节和自主神经功能，以确定其后遗症风险最大的人。 确定和测试催汗和血管收缩活动的神经控制机制 以确定它们的传出胆碱能控制是否是通过解剖学上独立的一组神经。（一） 在SCI患者热应激期间绘制血管扩张和催汗活动的区域，并比较 温度调节损伤水平（TLOI）与感觉运动LOI。(2)测试是否增加去甲肾上腺素能 血管收缩活性减弱了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动影响 在全身期间，SR和SkBF不一致的区域中的血管收缩和/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， 将概述催汗和血管活动的区域。使用溴苄铵离子电渗的药理学试验 将使用肉毒毒素皮内注射来操纵具有一致性和 不协调的血管扩张和催汗活动，以确定每个区域的神经控制机制。 将完整的体温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博士在未来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， 在该领域经验丰富的研究人员和临床医生的指导下，这个机会可以让她 发展必要的技能，以竞争在未来的VA优异评审奖。她的长期目标是 成为一名VA医生科学家，拥有一个独立资助的研究项目，这将使她能够 这对SCI后自主神经功能障碍领域目前尚未回答的问题做出了重要贡献。

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.