Lefèvre Chloë, Bessard Anne, Aubert Philippe, Joussain Charles, Giuliano François, Behr-Roussel Delphine, Perrouin-Verbe Marie-Aimée, Perrouin-Verbe Brigitte, Brochard Charlène, Neunlist Michel
UMR Inserm 1235, Research Unit, The Enteric Nervous System in Gut and Brain Diseases (TENS), University of Nantes, Nantes, France.
Neurological Physical and Rehabilitation Medicine Department, University Hospital of Nantes, Nantes, France.
Neurotrauma Rep. 2020 Oct 22;1(1):125-136. doi: 10.1089/neur.2020.0041. eCollection 2020.
The physiopathology of digestive disorders in patients with spinal cord injury (SCI) remains largely unknown, particularly the involvement of the enteric nervous system (ENS). We aimed in a rat model of chronic thoracic SCI to characterize (1) changes in the neurochemical coding of enteric neurons and their putative consequences upon neuromuscular response, and (2) the inflammatory response of the colon. motility of proximal and distal colon segments of SCI and control (CT) rats were studied in an organ chamber in response to electrical field stimulation (EFS) and bethanechol. Immunohistochemical analysis of proximal and distal segments was performed using antibodies again Hu, neuronal nitric oxide synthase, (nNOS), and choline acetyltransferase. Colonic content of acetylcholine and acetylcholinesterase was measured; messenger RNA (mRNA) expression of inflammatory cytokines was measured using reverse transcription quantitative polymerase chain reaction (RT-qPCR) approaches. Compared with the CT rats, the contractile response to bethanechol was significantly decreased in the proximal colon of SCI rats but not in the distal colon. The proportion of nNOS immunoreactive (IR) neurons was significantly reduced in the proximal but not distal colon of SCI rats. No change in proportion of choline acetyltransferase (ChAT)-IR was reported; the tissue concentration of acetylcholine was significantly decreased in the proximal colon of SCI rats. The expression of tumor necrosis factor alpha (TNF-α) and intercellular adhesion molecule-1 (ICAM-1) was significantly reduced in the proximal and distal colon of SCI rats. This study demonstrates that functional motor and enteric neuroplastic changes affect preferentially the proximal colon compared with the distal colon. The underlying mechanisms and factors responsible for these changes remain to be discovered.
脊髓损伤（SCI）患者消化系统疾病的生理病理学在很大程度上仍不清楚，尤其是肠神经系统（ENS）的受累情况。我们旨在通过慢性胸段SCI大鼠模型来表征：（1）肠神经元神经化学编码的变化及其对神经肌肉反应的可能影响，以及（2）结肠的炎症反应。在器官腔室中研究了SCI大鼠和对照（CT）大鼠近端和远端结肠段对电场刺激（EFS）和氨甲酰甲胆碱的运动反应。使用针对Hu、神经元型一氧化氮合酶（nNOS）和胆碱乙酰转移酶的抗体对近端和远端段进行免疫组织化学分析。测量结肠中乙酰胆碱和乙酰胆碱酯酶的含量；使用逆转录定量聚合酶链反应（RT-qPCR）方法测量炎症细胞因子的信使核糖核酸（mRNA）表达。与CT大鼠相比，SCI大鼠近端结肠对氨甲酰甲胆碱的收缩反应显著降低，但远端结肠未出现这种情况。SCI大鼠近端结肠中nNOS免疫反应性（IR）神经元的比例显著降低，但远端结肠未降低。胆碱乙酰转移酶（ChAT）-IR的比例未见变化；SCI大鼠近端结肠中乙酰胆碱的组织浓度显著降低。SCI大鼠近端和远端结肠中肿瘤坏死因子α（TNF-α）和细胞间黏附分子-1（ICAM-1）的表达显著降低。本研究表明，与远端结肠相比，功能性运动和肠神经可塑性变化对近端结肠的影响更为明显。导致这些变化的潜在机制和因素仍有待发现。
