Axonal plasticity is important for neurofunctional recovery after stroke. This study aimed to explore the role of transcutaneous auricular vagus nerve stimulation (ta-VNS) on axonal plasticity and its underlying association with the α7 nicotinic acetylcholine receptor(α7nAchR) after cerebral ischemia/reperfusion (I/R) injury. Adult male Sprague-Dawley rats were pretreated by intraperitoneal injection with either phosphate-buffered saline (PBS) or an α7nAchR antagonist and then subjected to middle cerebral artery occlusion and ta-VNS treatment. α7nAchR expression and localization in the peri-infarct cortex were examined after ta-VNS treatment. Subsequently, neurologic scores were assessed with a battery of tests. Axonal regeneration, indicated by upregulation of growth-associated protein 43 (GAP-43) and neurofilament protein 200 (NF-200), was assessed. Axonal reorganization was examined on the basis of anterograde movement of the neuronal molecular probe biotin dextran amine. Additionally, brain-derived neurotrophic factor (BDNF)-associated signaling was measured 28d after I/R. Our findings showed that ta-VNS treatment enhanced α7nAchR expression in the ischemic cortex. α7nAchR colocalized with DCX and Nestin after reperfusion. Furthermore, ta-VNS-treated I/R rats displayed enhanced neurobehavioral performance and increased axonal plasticity (axonal regeneration and axonal reorganization), as indicated by elevated levels of BDNF/cyclic AMP (cAMP)/protein kinase A (PKA)/phosphorylated cAMP response element-binding protein pathway (p-CREB) pathway members. Strikingly, the beneficial effects of ta-VNS were diminished after α7nAchR blockade. In conclusion, our study is the first to show that α7nAchR is a potential mediator of ta-VNS-induced neuroprotection in the chronic phase of stroke and that its effects may be related to enhanced axonal plasticity through activation of the BDNF/cAMP/PKA/p-CREB pathway.

中文翻译：

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α7nAchR通过增强轴突可塑性来介导缺血性中风大鼠模型的经皮耳迷走神经刺激引起的神经保护作用。

轴突可塑性对于中风后神经功能的恢复很重要。这项研究旨在探讨经皮耳廓迷走神经刺激（ta-VNS）对轴突可塑性的作用及其与脑缺血/再灌注（I / R）损伤后α7烟碱乙酰胆碱受体（α7nAchR）的潜在联系。成年雄性Sprague-Dawley大鼠通过腹腔注射磷酸盐缓冲液（PBS）或α7nAchR拮抗剂进行预处理，然后进行大脑中动脉闭塞和ta-VNS治疗。ta-VNS处理后，检查梗死周围皮层中α7nAchR的表达和定位。随后，通过一系列测试评估神经系统评分。轴突再生，以生长相关蛋白43（GAP-43）和神经丝蛋白200（NF-200）上调为标志，被评估。在神经元分子探针生物素葡聚糖胺的顺行运动的基础上检查了轴突重组。此外，在I / R后28天测量了脑源性神经营养因子（BDNF）相关信号。我们的发现表明，ta-VNS处理可增强缺血皮层中的α7nAchR表达。再灌注后，α7nAchR与DCX和Nestin共定位。此外，ta-VNS处理的I / R大鼠表现出增强的神经行为表现和轴突可塑性（轴突再生和轴突重组），如BDNF /环AMP（cAMP）/蛋白激酶A（PKA）/磷酸化cAMP水平升高所表明响应元件结合蛋白途径（p-CREB）途径成员。令人惊讶的是，α7nAchR阻断后，ta-VNS的有益作用减弱了。结论，