Program in Neuroscience, Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology, Washington State University, Pullman, WA 99164, USA.
Neurosci Lett. 2012 Mar 28;513(1):31-6. doi: 10.1016/j.neulet.2012.01.079. Epub 2012 Feb 10.
Damage to peripheral nerve branches triggers activation of microglia in CNS areas containing motor neuron soma and primary afferent terminals of the damaged fibers. Furthermore, microglial activation occurs in areas containing the soma and terminals of spared nerve branches of a damaged nerve. Because the abdominal viscera are innervated by spinal afferents as well as vagal afferents and efferents, we speculated that spinal nerves might respond like spared nerve branches following damage to vagal fibers. Therefore, we tested the hypothesis that damage to the abdominal vagus would result in microglial activation in vagal structures-the nucleus of the solitary tract (NTS), dorsal motor nucleus of the vagus nerve (DMV), and nodose ganglia (NG)-as well as spinal cord (SC) segments that innervate the abdominal viscera. To test this hypothesis, rats underwent subdiaphragmatic vagotomy or sham surgery and were treated with saline or the microglial inhibitor, minocycline. Microglial activation was determined by quantifying changes in the intensity of fluorescent staining with a primary antibody against ionizing calcium adapter binding molecule 1 (Iba1). We found that subdiaphragmatic vagotomy significantly activated microglia in the NTS, DMV, and NG two weeks post-vagotomy. Microglial activation remained significantly increased in the NG and DMV for at least 42 days. Surprisingly, vagotomy significantly decreased microglial activation in the SC. Minocycline treatment attenuated microglial activation in all studied areas. Our results indicate that microglial activation in vagal structures following abdominal vagal damage is accompanied by suppression of microglial activation in associated areas of the spinal cord.
外周神经分支的损伤会触发中枢神经系统（CNS）区域中运动神经元体和受损纤维的初级传入末端处的小胶质细胞激活。此外，小胶质细胞的激活发生在包含受损神经的未受损伤神经分支的体和末端的区域中。由于腹部内脏受脊髓传入神经以及迷走神经传入和传出神经的支配，我们推测，在迷走神经纤维损伤后，脊髓神经可能会像未受损伤的神经分支一样做出反应。因此，我们假设测试了以下假设：即腹部迷走神经的损伤会导致迷走神经结构（孤束核（NTS），迷走神经背核（DMV）和结状神经节（NG））以及支配腹部内脏的脊髓（SC）节段中的小胶质细胞激活。为了验证该假设，大鼠接受了膈下迷走神经切断术或假手术，并接受了生理盐水或小胶质细胞抑制剂米诺环素的治疗。通过定量分析针对离子钙接头结合分子 1（Iba1）的一抗的荧光染色强度来确定小胶质细胞的激活。我们发现，膈下迷走神经切断术在迷走神经切断后两周显着激活了 NTS、DMV 和 NG 中的小胶质细胞。NG 和 DMV 中的小胶质细胞激活至少持续 42 天。令人惊讶的是，迷走神经切断术显着降低了 SC 中的小胶质细胞激活。米诺环素治疗可减轻所有研究区域的小胶质细胞激活。我们的结果表明，腹部迷走神经损伤后迷走神经结构中小胶质细胞的激活伴随着脊髓相关区域中小胶质细胞激活的抑制。
