Α7nAchR mediates transcutaneous auricular vagus nerve stimulation-induced neuroprotection in a rat model of ischemic stroke by enhancing axonal plasticity. (21st June 2020)

• Record Type: Journal Article
• Authors: Li, Jiani; Zhang, Qinbin; Li, Sheng; Niu, Lingchuan; Ma, Jingxi; Wen, Lan; Zhang, Lina; Li, Changqing
• Is Part Of: Neuroscience letters. Volume 730(2020)
• Publication Date: 2020-06-21
• Subjects: Axonal plasticity -- α7nAchR -- BDNF -- MCAO/R -- ta-VNS; Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2020.135031
• Languages: English
• ISSNs: 0304-3940

Abstract

Highlights: Ta-VNS treatment boosted axon plasticity and improved long-term neurofunctional recovery following ischemic stroke. Ta-VNS treatment activated α7nAChR in the chronic phase of ischemic stroke. Blockade of α7nAChR attenuated the ta-VNS-mediated promotion of axonal plasticity and neuroprotection following ischemic stroke. Ta-VNS treatment boosted axonal plasticity and improved neurofunctional recovery through α7nAChR-mediated activation of BDNF-associated signaling pathways following ischemic stroke. Abstract: 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.