Gastric dysreflexia after spinal cord injury

描述(由申请人提供)：脊髓损伤(SCI)后立即阶段的临床报告表明，胃肠道淤滞或肠梗阻会导致吸入和反流的并发症。胃饲不耐受需要积极的全肠外营养，偶尔需要侵入性和胃肠道手术干预(伴随并发症的风险)，以维持正能量和氮平衡。伴随严重和长期胃淤滞而产生的吸入风险需要加强对呼吸道的管理，这是创伤后发病率和死亡率的一个重要原因。从最初的创伤稳定下来后，不同程度的这种综合征可能会持续很长时间，从而对患者脊髓损伤后的生活质量产生深远的负面影响。该项目的范围是利用PI建立的脊髓挫伤模型来研究脊髓损伤后的胃淤滞。胃的运动和排空在很大程度上是由副交感神经反射调节的，副交感神经反射通过迷走神经将一般内脏传入传入延髓。延髓对胃运动的控制通过迷走神经传出返回胃。脊髓损伤患者迷走-迷走神经反射在解剖学上保持完好。然而，损伤后的胃发病率表明，脊髓介导的延髓输入被破坏，导致有文献记载的延髓回路的兴奋，从而产生类似于迷走神经干切断术的痉挛性胃瘫。使用高位胸部损伤模型将最大限度地减少胃内脏传入DVC信息的脊髓中继站。通过这样做，将解决下列特定目标：1)T3挫伤将产生痉挛性胃瘫(即胃排空减少、弹性和动力降低)；2)确认脊髓损伤后上行脊髓屏障输入的丢失是胃反射改变的基础；3)确定脊髓上行纤维及其作用于脑干神经元的投射和神经化学表型；4)轻至中度脊髓损伤后，损伤后胃淤滞将表现出解剖学上的恢复。该实验室的长期目标是建立一种涵盖整个胃肠道长度的脊髓损伤后胃肠功能改变的模型，以缓解人类脊髓损伤患者的胃肠功能障碍。PI对脊髓损伤后远端肠道(肠)排空反射的研究，加上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.