Institute of Surgical Research, Albert Szent-Györgyi Medical and Pharmaceutical Centre, University of Szeged, P.O. Box 464, Szeged, 6701, Hungary.
J Neural Transm (Vienna). 2012 Feb;119(2):211-23. doi: 10.1007/s00702-011-0658-x. Epub 2011 May 27.
Gastrointestinal neuroprotection involves the net effect of many mechanisms which protect the enteral nervous system and its cells from death, dysfunction or degeneration. Neuroprotection is also a therapeutic strategy, aimed at slowing or halting the progression of primary neuronal loss following acute or chronic diseases. The neuroprotective properties of a compound clearly have implications for an understanding of the mechanism of dysfunctions and for therapeutic approaches in a number of gastrointestinal diseases.This paper focused on the roles of glutamate and N-methyl-D-aspartate (NMDA) receptors in the intrinsic neuronal control of gastrointestinal motility; the consequences of inflammation on gastrointestinal motility changes; and the involvement of tryptophan metabolites (especially kynurenic acid) in the regulatory function of the enteral nervous system and the modulation of the inflammatory response. Common features in the mechanisms of action, illustrative evidence from animal models, and experimental neuroprotective therapies making use of the currently available possibilities are also discussed.Overall, the evidence suggests that gastrointestinal neuroprotection against inflammation and glutamate-induced neurotoxicity may be mediated synergistically through the blockade of NMDA receptors and the inhibition of neuronal nitric oxide synthase activity and xanthine oxidoreductase-dependent superoxide production. These components are likewise significant factors in the pathomechanism of gastrointestinal inflammatory diseases and inflammation-linked motility alterations. Inhibition of the enteric NMDA receptors by kynurenic acid or its analogues may provide a novel option via which to influence intestinal hypermotility and inflammatory processes simultaneously.
胃肠道神经保护涉及许多机制的净效应，这些机制可保护肠神经系统及其细胞免于死亡、功能障碍或退化。神经保护也是一种治疗策略，旨在减缓或阻止急性或慢性疾病后原发性神经元丧失的进展。一种化合物的神经保护特性显然对理解功能障碍的机制以及许多胃肠道疾病的治疗方法具有重要意义。本文重点介绍了谷氨酸和 N-甲基-D-天冬氨酸 (NMDA) 受体在胃肠道运动的固有神经元控制中的作用；炎症对胃肠道运动变化的影响；以及色氨酸代谢物（特别是犬尿氨酸）在肠神经系统的调节功能中的作用，以及对炎症反应的调节。还讨论了作用机制中的共同特征、来自动物模型的说明性证据以及利用当前可用可能性进行的实验性神经保护治疗。总的来说，有证据表明，针对炎症和谷氨酸诱导的神经毒性的胃肠道神经保护可能通过 NMDA 受体阻断以及抑制神经元一氧化氮合酶活性和黄嘌呤氧化还原酶依赖性超氧化物产生而协同介导。这些成分同样是胃肠道炎症性疾病和炎症相关运动改变的发病机制中的重要因素。犬尿氨酸或其类似物对肠 NMDA 受体的抑制可能通过同时影响肠道过度运动和炎症过程提供一种新的选择。
