title: Vagus nerve stimulation attenuates cerebral ischemia and reperfusion injury via endogenous cholinergic pathway in rat.
abstract: Inflammation and apoptosis play critical roles in the acute progression of ischemic injury pathology. Emerging evidence indicates that vagus nerve stimulation (VNS) following focal cerebral ischemia and reperfusion (I/R) may be neuroprotective by limiting infarct size. However, the underlying molecular mechanisms remain unclear. In this study, we investigated whether the protective effects of VNS in acute cerebral I/R injury were associated with anti-inflammatory and anti-apoptotic processes. Male Sprague-Dawley (SD) rats underwent VNS at 30 min after focal cerebral I/R surgery. Twenty-four h after reperfusion, neurological deficit scores, infarct volume, and neuronal apoptosis were evaluated. In addition, the levels of pro-inflammatory cytokines were detected using enzyme-linked immune sorbent assay (ELISA), and immunofluorescence staining for the endogenous "cholinergic anti-inflammatory pathway" was also performed. The protein expression of a7 nicotinic acetylcholine receptor (a7nAchR), phosphorylated Akt (p-Akt), and cleaved caspase 3 in ischemic penumbra were determined with Western blot analysis. I/R rats treated with VNS (I/R+VNS) had significantly better neurological deficit scores, reduced cerebral infarct volume, and decreased number of TdT mediated dUTP nick end labeling (TUNEL) positive cells. Furthermore, in the ischemic penumbra of the I/R+VNS group, the levels of pro-inflammatory cytokines and cleaved caspase 3 protein were significantly decreased, and the levels of a7nAchR and phosphorylated Akt were significantly increased relative to the I/R alone group. These results indicate that VNS is neuroprotective in acute cerebral I/R injury by suppressing inflammation and apoptosis via activation of cholinergic and a7nAchR/Akt pathways.
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Longling
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Changqing
authors.initials: C
authors.lastname: Li
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D002545:Brain Ischemia / Q000150:complications*; D002560:Cerebrovascular Circulation; D016207:Cytokines / Q000378:metabolism; D005786:Gene Expression Regulation; D008297:Male; D017628:Microglia / Q000378:metabolism; D009474:Neurons / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy*; D015398:Signal Transduction; D055536:Vagus Nerve Stimulation; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000378:metabolism
chemical_list: D016207:Cytokines; D064569:alpha7 Nicotinic Acetylcholine Receptor; D051057:Proto-Oncogene Proteins c-akt; D000109:Acetylcholine