Vagus Nerve Stimulation with Mild Stimulation Intensity Exerts Anti-Inflammatory and Neuroprotective Effects in Parkinson’s Disease Model Rats
Ittetsu Kin, Tatsuya Sasaki, Takao Yasuhara, Masahiro Kameda, Takashi Agari, Mihoko Okazaki, Kakeru Hosomoto, Yosuke Okazaki, Satoru Yabuno, Satoshi Kawauchi, Ken Kuwahara, Jun Morimoto, Kyohei Kin, Michiari Umakoshi, Yousuke Tomita, Naoki Tajiri, Cesar V. Borlongan, Isao Date
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.