Vagus nerve stimulation during rehabilitative training enhances recovery of forelimb function after ischemic stroke in aged rats

Abstract

Advanced age is associated with a higher incidence of stroke and worse functional outcomes. Vagus nerve stimulation (VNS) paired with rehabilitative training has emerged as a potential method to improve recovery after brain injury but to date has only been evaluated in young rats. Here, we evaluated whether VNS paired with rehabilitative training would improve recovery of forelimb function after ischemic lesion of the motor cortex in rats 18 months of age. Rats were trained to perform the isometric pull task, an automated, quantitative measure of volitional forelimb strength. Once proficient, rats received an ischemic lesion of the motor cortex and underwent rehabilitative training paired with VNS for 6 weeks. VNS paired with rehabilitative training significantly enhances recovery of forelimb function after lesion. Rehabilitative training without VNS results in a 34% ± 19% recovery, whereas VNS paired with rehabilitative training yields a 98% ± 8% recovery of prelesion of forelimb function. VNS does not significantly reduce lesion size. These findings demonstrate that VNS paired with rehabilitative training enhances motor recovery in aged subjects in a model of stroke and may suggest that VNS therapy may effectively translate to elderly stroke patients.

Parametric characterization of neural activity in the locus coeruleus in response to vagus nerve stimulation

“…Preclinical studies demonstrate that VNS paired with rehabilitative training improves recovery in models of tinnitus, ischemic and hemorrhagic stroke, and traumatic brain injury (Engineer et al, 2011, Khodaparast et al, 2013, Khodaparast et al, 2014, Hays et al, 2014, Pruitt et al, 2016, Khodaparast et al, 2016, Hays et al, 2016). Moreover, clinical studies provide an initial indication of the clinical utility of VNS-based plasticity therapies for tinnitus and stroke patients (Dawson et al, 2016, De Ridder et al, 2014).…”

“…Body temperature was maintained throughout surgery and neural recording using a feedback-controlled electric warming pad (FHC, Bowdoin, ME). Subjects were implanted with a custom made platinum-iridium bipolar stimulating cuff electrode on the left cervical vagus nerve, as previously described (Engineer et al, 2011, Khodaparast et al, 2013, Khodaparast et al, 2014, Hays et al, 2014, Pruitt et al, 2016, Khodaparast et al, 2016, Hays et al, 2016, Hulsey et al, 2016). A transient drop in blood oxygen saturation in response to a short (~3 sec) VNS train was used to confirm that the cuff electrode was functional.…”

Anatomo-Physiologic Basis for Auricular Stimulation

“…32,33 In this light, an increasing number of studies have shown that TNS is beneficial for seizure control, depression, and migraine, and, very recently, the FDA approved a clinical trial for TNS treatment of Lennox-Gastaut syndrome. 34 In addition to epilepsy and depression, researchers have proposed a clinical application for VNS and TNS for treating variety of disorders, such as migraine, 35 anxiety, 36 cognitive impairment, 37,38 Alzheimer's disease, 39 autism, 40 tinnitus, 41,42 poststroke symptoms, [43][44][45] post-traumatic stress disorder, 46 eating disorders 47 and obesity. 48 Although clinical trials on the topic are accumulating, most of them are preliminary proof-ofconcept pilot studies obtained with limited sample sizes.…”

Short-term Effects of Vagus Nerve Stimulation on Learning and Evoked Activity in Auditory Cortex

“…Previous studies have demonstrated that VNS during rehabilitative training improves recovery of motor function in several models of brain injury (Khodaparast et al, 2016, 2014; Hays et al, 2014a,b, 2016; Meyers et al, 2018; Morrison et al, 2019). The therapeutic effects of pairing VNS with motor rehabilitation persist even after the cessation of stimulation, suggesting that the VNS-induced plasticity and learning are long-term (Khodaparast et al, 2014; Hays et al, 2014a).…”