Multipronged approach to diminish sympathetic hyperreflexia and ensuing cardiovascular and immune dysfunction after spinal cord injury

多管齐下减少脊髓损伤后交感神经反射亢进和随之而来的心血管和免疫功能障碍

• 批准号: 10598487
• 负责人: Veronica Jean Tom
• 金额: $ 42.85万
• 依托单位: DREXEL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10598487
• 关键词: Affect; American; Animals; Autonomic Dysfunction; Autonomic Dysreflexia; Axon; Bacterial Pneumonia; Bladder; Blood; Brain Stem; Cardiovascular Diseases; Cardiovascular Physiology; Cardiovascular system; Chest; Chronic; Collaborations; Contusions; Disparate; Event; Fiber; Functional disorder; Hyperreflexia; Hypertension; Immune System Diseases; Immune system; Immunity; Immunologic Deficiency Syndromes; Immunosuppression; Individual; Infection; Injury; Interruption; Life; Mediating; Modeling; Morbidity - disease rate; Neurons; Organ; Output; Peptides; Persons; Physiological; Play; Predisposition; Prophylactic treatment; Public Health; Recovery of Function; Regulation; Rodent; Role; Secondary to; Serotonin; Severities; Signal Transduction; Silver; Spinal; Spinal Cord; Spinal cord injury; Spleen; Sympathetic Nervous System; System; TNF gene; Testing; Therapeutic; Tissues; Transplantation; Vertebral column; antagonist; cardiovascular infection; clinically relevant; cytokine; efficacy evaluation; experimental study; hemodynamics; immune function; improved; injured; mind control; mortality; nerve supply; prevent; receptor; response; tumor necrosis factor-alpha inhibitor

PROJECT SUMMARY Spinal cord injury (SCI) is a devastating event sustained by as many as 1.3 million Americans. While not often appreciated, cardiovascular disease and susceptibility to infection are leading causes of mortality and morbidity in individuals living with SCI. One major reason thought to underlie these issues is SCI-induced dysregulation of the sympathetic nervous system. In this proposal, we will use a clinically-relevant contusion rodent SCI model to test the hypothesis that intracellular sigma peptide (ISP) will promote sufficient sprouting of serotonergic axons onto neurons in the spinal sympathetic circuit below the SCI to normalize sympathetic activity after injury. Furthermore, we hypothesize that administering a combining ISP and inhibition of soluble tumor necrosis factor alpha (sTNFα) with XPro1595 – which target different root causes of sympathetic hyperreflexia after SCI (i.e., interrupted supraspinal input the spinal sympathetic circuit and sTNFα-induced maladaptive plasticity of the spinal sympathetic circuit, respectively) – will have synergistic effects on improving cardiovascular and immune function after SCI.

项目摘要 脊髓损伤（SCI）是由多达130万美国人承担的毁灭性事件。虽然不经常 值得赞赏的是心血管疾病和感染的敏感性是死亡率和发病率的主要原因 在科幻的人中。这些问题是基于这些问题的主要原因是Sci引起的失调 交感神经系统。在此提案中，我们将使用与临床上的浓度啮齿动物SCI模型 为了测试细胞内sigma肽（ISP）将促进足够发芽的假说 SCI以下脊柱交感神经回路的轴突上的神经元，以使损伤后的交感神经活动正常化。 此外，我们假设给予ISP组合和抑制实体肿瘤坏死因子 具有XPRO1595的alpha（STNFα） - 靶向SCI后的不同根本原因（即 脊柱上断脊柱交感神经回路和STNFα诱导的不良适应性可塑性 脊柱交感神经回路） - 将对改善心血管和免疫产生协同作用 科学后的功能。