Objective: To assess the therapeutic potential of chronic vagus nerve stimulation (VNS) to attenuate the behavioral and neuronal deficits observed in Parkinson’s disease (PD) by increasing brain derived neurotrophic factor (BDNF) and endogenous antioxidants.

Background: Existing treatment strategies for PD progressively become ineffective and produce debilitating side effects, such as L-dopa induced dyskinesia. In PD, locus coeruleus noradrenergic neurons (LC-NE) degenerate prior to substantia nigra dopaminergic (SN-DA) neuron loss. VNS (FDA-approved for epilepsy and depression) increases firing rates of LC-NE neurons, as well as increases BDNF in the LC and its target regions, making it a potential PD therapeutic. VNS has also been shown to exert antioxidant effects by increasing endogenous antioxidants, such as glutathione, and reducing oxidative stress after cerebral ischemia.

Methods: We utilized a double-lesion rat model of PD by administering the NE neurotoxin DSP-4, followed by an intrastriatal DA lesion one week later using 6-OHDA. Immediately after 6-OHDA, vagus nerve cuffs were implanted into a subset of rats. Beginning ten days post-DA lesion, animals received a precise VNS regimen twice a day for two weeks at a set amplitude and rate, measuring locomotor activity during the afternoon session each day. Immediately following the final stimulation, rats were euthanized, the left dorsal striatum, bilateral SN and LC were sectioned for immunohistochemical detection of tyrosine hydroxylase (TH), and the right frontal cortex, hippocampus, and dorsal striatum were dissected and processed for BDNF content and glutathione detection.

Results: Locomotor activity was significantly increased in lesioned rats that underwent VNS compared to non-stimulated lesioned rats. VNS treatment also significantly increased numbers of TH-positive neurons in the SN and LC, increased BDNF in the frontal cortex and dorsal striatum, and elevated glutathione levels in the dorsal striatum compared to non-stimulated lesioned rats.

Conclusions: These data suggest the potential of VNS as a novel therapeutic for PD, and support the idea that neuroprotection is mediated in LC-NE and SN-DA neuronal populations via BDNF and antioxidant mechanisms. Furthermore, the use of VNS therapy would alleviate stress and anxiety associated with intracranial implantation for Deep Brain Stimulation.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/vagus-nerve-stimulation-as-a-novel-treatment-strategy-for-parkinsons-disease/