Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA 70808, USA.
Neurogastroenterol Motil. 2011 Feb;23(2):e69-79. doi: 10.1111/j.1365-2982.2010.01616.x. Epub 2010 Oct 18.
We have shown recently that our model of experimental high-thoracic spinal cord injury (T3-SCI) mirrors the gastrointestinal clinical presentation of neurotrauma patients, whereby T3-SCI animals show diminished gastric emptying and dysmotility. In this study we used cholecystokinin as a model peptide to test the hypothesis that the T3-SCI induced gastroparesis is due, in part, to an impaired vagally-mediated response to gastrointestinal peptides.
We measured the responses to sulfated cholecystokinin (CCK-8s) in control and T3-SCI (3 or 21 days after injury) rats utilizing: (i) c-fos expression in the nucleus tractus solitarius (NTS) following peripherally administered CCK-8s; (ii) in vivo gastric tone and motility following unilateral microinjection of CCK-8s into the dorsal vagal complex (DVC); and (iii) whole cell recordings of glutamatergic synaptic inputs to NTS neurons.
Our results show that: (i) medullary c-fos expression in response to peripheral CCK-8s was significantly lower in T3-SCI rats 3 days after the injury, but recovered to control values at 3 weeks post-SCI, (ii) Unilateral microinjection of CCK-8s in the DVC induced a profound gastric relaxation in control animals, but did not induce any response in T3-SCI rats at both 3 and 21 days after SCI, (iii) Perfusion with CCK-8s increased glutamatergic currents in 55% of NTS neurons from control rats, but failed to induce any response in NTS neurons from T3-SCI rats.
CONCLUSIONS & INFERENCES: Our data indicate alterations of vagal responses to CCK-8s in T3-SCI rats that may reflect a generalized impairment of gastric vagal neurocircuitry, leading to a reduction of gastric functions after SCI.
我们最近表明，我们的实验性高胸脊髓损伤（T3-SCI）模型反映了神经创伤患者的胃肠道临床表现，其中 T3-SCI 动物表现出胃排空减少和运动障碍。在这项研究中，我们使用胆囊收缩素作为模型肽来检验假设，即 T3-SCI 诱导的胃轻瘫部分是由于胃肠道肽的迷走神经介导反应受损。
我们使用以下方法测量了对硫酸胆囊收缩素（CCK-8s）的反应：（i）在外周给予 CCK-8s 后，在孤束核（NTS）中测量 c-fos 表达；（ii）单侧微注射 CCK-8s 到迷走神经复合体（DVC）后，测量胃张力和运动；（iii）NTS 神经元的谷氨酸能突触输入的全细胞记录。
我们的结果表明：（i）T3-SCI 大鼠在损伤后 3 天，对周围 CCK-8s 的髓质 c-fos 表达明显降低，但在 SCI 后 3 周恢复到对照值；（ii）单侧微注射 CCK-8s 到 DVC 在对照动物中诱导了深刻的胃松弛，但在 T3-SCI 大鼠中在 SCI 后 3 天和 21 天都没有诱导任何反应；（iii）CCK-8s 的灌流增加了 55%来自对照大鼠的 NTS 神经元的谷氨酸电流，但未能诱导来自 T3-SCI 大鼠的 NTS 神经元的任何反应。
我们的数据表明，T3-SCI 大鼠中迷走神经对 CCK-8s 的反应发生改变，这可能反映了胃迷走神经神经回路的普遍损伤，导致 SCI 后胃功能下降。
