MDPI Acta Medica Okayama 2227-9059 9 7 2021 Vagus Nerve Stimulation with Mild Stimulation Intensity Exerts Anti-Inflammatory and Neuroprotective Effects in Parkinson's Disease Model Rats 789 EN Ittetsu Kin Department of Neurological Surgery, Okayama University Graduate School of Medicine Tatsuya Sasaki Department of Neurological Surgery, Okayama University Graduate School of Medicine Takao Yasuhara Department of Neurological Surgery, Okayama University Graduate School of Medicine Masahiro Kameda Department of Neurological Surgery, Okayama University Graduate School of Medicine Takashi Agari Department of Neurosurgery, Tokyo Metropolitan Neurological Hospital Mihoko Okazaki Department of Neurological Surgery, Okayama University Graduate School of Medicine Kakeru Hosomoto Department of Neurological Surgery, Okayama University Graduate School of Medicine Yosuke Okazaki Department of Neurological Surgery, Okayama University Graduate School of Medicine Satoru Yabuno Department of Neurological Surgery, Okayama University Graduate School of Medicine Satoshi Kawauchi Department of Neurological Surgery, Okayama University Graduate School of Medicine Ken Kuwahara Department of Neurological Surgery, Okayama University Graduate School of Medicine Jun Morimoto Department of Neurological Surgery, Okayama University Graduate School of Medicine Kyohei Kin Department of Neurological Surgery, Okayama University Graduate School of Medicine Michiari Umakoshi Department of Neurological Surgery, Okayama University Graduate School of Medicine Yousuke Tomita Department of Neurological Surgery, Okayama University Graduate School of Medicine Naoki Tajiri Department of Neurophysiology and Brain Science and Medical School, Graduate School of Medical Sciences and Medical School, Nagoya City University Cesario, V Borlongan Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, 12901 Bruce B. Downs Blvd. Isao Date Department of Neurological Surgery, Okayama University Graduate School of Medicine 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. No potential conflict of interest relevant to this article was reported.