Gastric dysreflexia after spinal cord injury

描述（由申请方提供）：脊髓损伤（SCI）后即刻阶段的临床报告表明，胃肠道淤滞或肠梗阻会导致误吸和反流并发症。胃饲不耐受需要积极的全胃肠外营养，偶尔需要侵入性和GI手术干预（伴有并发症风险），以维持正能量和氮平衡。伴随严重和长期胃郁滞的误吸风险需要气道的强化管理，并且是创伤后发病率和死亡率的重要原因。不同程度的这种综合征可能会持续很长时间，从最初的创伤稳定，从而对SCI后患者的生活质量有深远的负面影响。该项目的范围是使用PI建立的技术，使用脊柱挫伤的高位胸椎（脊柱水平T3）模型研究SCI后胃潴留。胃运动和排空主要由副交感神经反射介导，副交感神经反射通过迷走神经将一般内脏传入输入并入延髓。胃运动的延髓控制通过迷走神经传出返回到胃。这种迷走神经-迷走神经反射在SCI患者中保持解剖学完整。然而，损伤后的胃发病率表明，脊髓介导的输入到延髓被破坏，导致在一个激励的记录良好的延髓电路，产生痉挛性胃轻瘫类似于迷走神经干切断术。使用高位胸部损伤模型将最大限度地减少胃内脏传入信息到DVC的脊髓中继。这样做将解决以下具体目的：1）T3挫伤损伤将产生痉挛性胃麻痹（即，胃排空、弹性和运动性降低）; 2）确定上行脊髓孤束输入的丧失是SCI后胃反射改变的基础; 3）确定上行脊髓孤束纤维及其作用的脑干神经元的投射和神经化学表型; 4）轻度至中度SCI后，损伤后胃停滞将随着时间的推移而表现出解剖学恢复。本实验室的长期目标是建立一个SCI后胃肠道功能改变的模型，包括整个胃肠道的长度，以减轻人类SCI患者的胃肠道功能障碍。PI对SCI后远端肠道（肠）消除反射的研究，与Co-I对胃功能脑干调节的研究显然是互补的。

DESCRIPTION (provided by applicant): Clinical reports of the immediate post-spinal cord injury (SCI) phase indicate that gastrointestinal stasis, or ileus, results in complications from aspiration and reflux. Gastric feeding intolerance necessitates aggressive total parenteral nutrition and occasionally invasive and GI surgical intervention (with associated risk of complications) for the maintenance of a positive energy and nitrogen balance. The resultant risk of aspiration that accompanies severe and prolonged gastric stasis requires intensive management of the airway and is a significant cause of post-trauma morbidity and mortality. Various degrees of this syndrome may continue long after stabilization from the initial trauma thus having profound negative effects on the patient's quality of life after SCI. The scope of the project is to use a high thoracic (spinal level T3) model of spinal contusion injury using established techniques by the PI to the study of post-SCI gastric stasis. Gastric motility and emptying is heavily mediated by parasympathetic reflexes that incorporate general visceral afferent input to the medulla via the vagus nerve. Medulary control of gastric motility returns to the stomach via vagal efferents. This vago-vagal reflex remains anatomically intact in the SCI patient. However, the post-injury gastric morbidity suggests that a spinally-mediated input to the medulla is disrupted, resulting in an excitation of well documented medullary circuits that produce a spastic gastroparesis similar to truncal vagotomy. Use of a high thoracic injury model will maximize the reduction in spinal relays for gastric visceral afferent information to the DVC. In so doing the following Specific Aims will be addressed 1) T3 contusion lesion will produce a spastic gastric paralysis (i.e., reduced gastric emptying, elastance, and motility); 2) Identify that the loss of ascending spinosolitary inputs is the basis for alterations in gastric reflexes after SCI; 3) Identify the projections and neurochemical phenotypes of the ascending spinosolitary fibers and the brainstem neurons upon which they act; 4) After mild to moderate SCI, post-injury gastric stasis will demonstrate anatomical recovery overtime. The long term goal of this laboratory is to establish a model of post-SCI alterations in gastrointestinal function that encompasses the entire length of the GI tract in order to alleviate GI dysfunction in human SCI patients. The PI's research on distal gut (bowel) eliminative reflexes after SCI, coupled with the Co-I's research on brainstem regulation of gastric function is clearly complementary.