Jiang Ying, Li Longling, Ma Jingxi, Zhang Lina, Niu Fei, Feng Tao, Li Changqing
Department of Neurology, Center for Neurodegenerative Disease, Beijing Tiantan Hospital, Capital Medical University, #6 Tian Tan Xi Li Street, Beijing 100050, China; China National Clinical Research Center for Neurological Diseases, #6 Tian Tan Xi Li Street, Beijing 100050, China.
Department of Neurology, Zhongshan Hospital, Xiamen University, #209 Hu Bin Nan Road, Xiamen, Fujian 361004, China.
Neurochem Int. 2016 Jul;97:73-82. doi: 10.1016/j.neuint.2016.02.009. Epub 2016 Mar 8.
Electrical stimulation of the vagus nerve, which has been used to treat epilepsy patients since 1997, also enhances long-term restoration after central nervous system (CNS) injury. Angiogenesis is a complex restorative mechanism that occurs in response to ischemic stroke, and it positively affects the recovery of neurological functions in a rat model of stroke. The aims of our study were to determine whether auricular vagus nerve stimulation (aVNS) promoted functional recovery and enhanced angiogenesis in the ischemic boundary following ischemia/reperfusion and to uncover the possible molecular mechanisms that are involved. Adult male Sprague-Dawley (SD) rats underwent transient middle cerebral artery occlusion (tMCAO) surgery and received repeated electrical stimulation of the left cavum concha starting 30 min after ischemia. For the following 21 days, we evaluated functional recovery at different time points using neurological deficit scores, the beam-walking test and the staircase test. The infarct volume was measured using TTC staining at 24 h post reperfusion, neuronal survival in the ischemic penumbra was assessed using hematoxylin and eosin (HE) staining. Microvessel density and endothelial cell proliferation in the ischemic boundary were assessed using immunofluorescence. The expression levels of brain-derived neurotrophic factor (BDNF), endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) in the ischemic penumbra were also evaluated. Our results showed that aVNS had significant neuroprotective effects and enhanced angiogenesis, which was demonstrated by improvements in the behavioral scores and brain histopathology, including increased levels of microvessel density and endothelial cell proliferation surrounding the infarct area. Furthermore, BDNF, eNOS and VEGF were expressed at higher levels in the I/R + aVNS group than in the I/R group or the I/R + sham aVNS group (p < 0.05). Our findings suggest that repeated aVNS promoted post-ischemic functional recovery and angiogenesis, possibly in conjunction with the up-regulated expression of BDNF, eNOS and VEGF in the rat brain.
自1997年以来，迷走神经电刺激已被用于治疗癫痫患者，它还能促进中枢神经系统（CNS）损伤后的长期恢复。血管生成是一种复杂的修复机制，发生在缺血性中风后，它对中风大鼠模型的神经功能恢复有积极影响。我们研究的目的是确定耳迷走神经刺激（aVNS）是否能促进缺血/再灌注后缺血边界的功能恢复并增强血管生成，并揭示其中可能涉及的分子机制。成年雄性Sprague-Dawley（SD）大鼠接受短暂性大脑中动脉闭塞（tMCAO）手术，并在缺血30分钟后开始对左侧耳甲腔进行重复电刺激。在接下来的21天里，我们在不同时间点使用神经功能缺损评分、走梁试验和阶梯试验评估功能恢复情况。在再灌注后24小时使用TTC染色测量梗死体积，使用苏木精和伊红（HE）染色评估缺血半暗带中的神经元存活情况。使用免疫荧光评估缺血边界中的微血管密度和内皮细胞增殖情况。还评估了缺血半暗带中脑源性神经营养因子（BDNF）、内皮型一氧化氮合酶（eNOS）和血管内皮生长因子（VEGF）的表达水平。我们的结果表明，aVNS具有显著的神经保护作用并增强了血管生成，这通过行为评分和脑病理学的改善得到证实，包括梗死区域周围微血管密度和内皮细胞增殖水平的增加。此外，BDNF、eNOS和VEGF在I/R + aVNS组中的表达水平高于I/R组或I/R + 假aVNS组（p < 0.05）。我们的研究结果表明，重复的aVNS促进了缺血后的功能恢复和血管生成，可能与大鼠脑中BDNF、eNOS和VEGF表达上调有关。
