start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=7 article-no= start-page=789 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210707 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Vagus Nerve Stimulation with Mild Stimulation Intensity Exerts Anti-Inflammatory and Neuroprotective Effects in Parkinson's Disease Model Rats en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: The major surgical treatment for Parkinson's disease (PD) is deep brain stimulation (DBS), but a less invasive treatment is desired. Vagus nerve stimulation (VNS) is a relatively safe treatment without cerebral invasiveness. In this study, we developed a wireless controllable electrical stimulator to examine the efficacy of VNS on PD model rats. Methods: Adult female Sprague-Dawley rats underwent placement of a cuff-type electrode and stimulator on the vagus nerve. Following which, 6-hydroxydopamine (6-OHDA) was administered into the left striatum to prepare a PD model. VNS was started immediately after 6-OHDA administration and continued for 14 days. We evaluated the therapeutic effects of VNS with behavioral and immunohistochemical outcome assays under different stimulation intensity (0.1, 0.25, 0.5 and 1 mA). Results: VNS with 0.25-0.5 mA intensity remarkably improved behavioral impairment, preserved dopamine neurons, reduced inflammatory glial cells, and increased noradrenergic neurons. On the other hand, VNS with 0.1 mA and 1 mA intensity did not display significant therapeutic efficacy. Conclusions: VNS with 0.25-0.5 mA intensity has anti-inflammatory and neuroprotective effects on PD model rats induced by 6-OHDA administration. In addition, we were able to confirm the practicality and effectiveness of the new experimental device. en-copyright= kn-copyright= en-aut-name=KinIttetsu en-aut-sei=Kin en-aut-mei=Ittetsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SasakiTatsuya en-aut-sei=Sasaki en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YasuharaTakao en-aut-sei=Yasuhara en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KamedaMasahiro en-aut-sei=Kameda en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AgariTakashi en-aut-sei=Agari en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OkazakiMihoko en-aut-sei=Okazaki en-aut-mei=Mihoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HosomotoKakeru en-aut-sei=Hosomoto en-aut-mei=Kakeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkazakiYosuke en-aut-sei=Okazaki en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YabunoSatoru en-aut-sei=Yabuno en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KawauchiSatoshi en-aut-sei=Kawauchi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KuwaharaKen en-aut-sei=Kuwahara en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MorimotoJun en-aut-sei=Morimoto en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KinKyohei en-aut-sei=Kin en-aut-mei=Kyohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=UmakoshiMichiari en-aut-sei=Umakoshi en-aut-mei=Michiari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TomitaYousuke en-aut-sei=Tomita en-aut-mei=Yousuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TajiriNaoki en-aut-sei=Tajiri en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=BorlonganCesario, V en-aut-sei=Borlongan en-aut-mei=Cesario, V kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=DateIsao en-aut-sei=Date en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Neurosurgery, Tokyo Metropolitan Neurological Hospital kn-affil= affil-num=6 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine kn-affil= affil-num=10 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine kn-affil= affil-num=13 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine kn-affil= affil-num=14 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine kn-affil= affil-num=15 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine kn-affil= affil-num=16 en-affil=Department of Neurophysiology and Brain Science and Medical School, Graduate School of Medical Sciences and Medical School, Nagoya City University kn-affil= affil-num=17 en-affil=Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, 12901 Bruce B. Downs Blvd. kn-affil= affil-num=18 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine kn-affil= en-keyword=anti-inflammation kn-keyword=anti-inflammation en-keyword=less invasive therapy kn-keyword=less invasive therapy en-keyword=new experimental device kn-keyword=new experimental device en-keyword=Parkinson's disease kn-keyword=Parkinson's disease en-keyword=vagus nerve stimulation kn-keyword=vagus nerve stimulation END