Vagus Nerve Stimulation During Rehabilitative Training Improves Forelimb Recovery After Chronic Ischemic Stroke in Rats

Abstract

Background and Objective Stroke is a leading cause of long-term disability. Currently, there are no consistently effective rehabilitative treatments for chronic stroke patients. Our recent studies demonstrate that VNS paired with rehabilitative training improves recovery of function in multiple models of stroke. Here, we evaluated the ability of VNS paired with rehabilitative training to improve recovery of forelimb strength when initiated many weeks after a cortical and subcortical ischemic lesion in subjects with stable, chronic motor deficits. Methods Rats were trained to perform an automated, quantitative measure of voluntary forelimb strength. Once proficient, rats received injections of endothelin-1 to cause a unilateral cortical and subcortical ischemic lesion. Six weeks after lesion, rats underwent rehabilitative training paired with VNS (Paired VNS; n = 10), rehabilitative training with equivalent VNS delivered two hours after daily rehabilitative training (Delayed VNS; n = 10), or rehabilitative training without VNS (Rehab, n = 9). Results VNS paired with rehabilitative training significantly improved recovery of forelimb function compared to control groups. The Paired VNS group displayed an 86% recovery of strength, the Rehab group exhibited 47% recovery, and the Delayed VNS group exhibited 42% recovery. Improvement in forelimb function was sustained in the Paired VNS group after the cessation of stimulation, potentially indicating lasting benefits. No differences in intensity of rehabilitative training, lesion size, or MAP-2 expression were observed between groups. Conclusion VNS paired with rehabilitative training confers significantly greater recovery of forelimb function after chronic ischemic stroke in rats.

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

“…No VNS was delivered on the sixth week, to allow assessment of persistent effects of VNS pairing. The 5-week course of VNS pairing is similar to previous studies (Hays et al, 2014a, 2014b; Khodaparast et al, 2013, 2014, 2015; Pruitt et al, 2015). …”

“…VNS paired with rehabilitative training enhances recovery of forelimb function in multiple models of brain injury in young rats (Hays et al, 2014a, 2014b; Khodaparast et al, 2013, 2014, 2015; Pruitt et al, 2015); therefore, we sought to examine whether VNS-dependent benefits would extend to aged subjects. Similar to previous studies, the present design evaluated VNS delivery to enhance the benefits of rehabilitative training (Hays et al, 2014a, 2014b; Khodaparast et al, 2013, 2014, 2015; Pruitt et al, 2015).…”

“…Vagus nerve stimulation (VNS) is believed to increase recovery by supporting neuroplasticity to enhance the benefits of rehabilitative training (Hays et al, 2013; Porter et al, 2011). VNS paired with rehabilitative training improves recovery of forelimb movement speed and volitional strength compared to rehabilitative training without VNS in models of cortical ischemic stroke (Hays et al, 2014b; Khodaparast et al, 2013, 2014) and even when initiated several weeks after lesion in a model of cortical and subcortical ischemic stroke (Khodaparast et al, 2015). Extending these findings, VNS therapy improves recovery in models of severe striatal intracerebral hemorrhage and traumatic brain injury (Hays et al, 2014a; Pruitt et al, 2015).…”

The supination assessment task: An automated method for quantifying forelimb rotational function in rats

“…Unilateral motor cortex ischemic lesions were administered similar to previously described (Hays et al 2013a, 2013b, 2014; Khodaparast et al 2013, 2014, 2015; Sloan et al 2015). Rats were anesthetized with ketamine hydrochloride (80mg/kg, i.p.)…”

Enhancing Rehabilitative Therapies with Vagus Nerve Stimulation

“…A study conducted by Khodaparast et al [66] sought to evaluate whether VNS paired with rehabilitative training would be effective after a long delay between ischemic lesion and therapy initiation. To this end, rats were trained to proficiency on the isometric force task and received an ischemic lesion of the motor cortex and dorsolateral striatum to impair use of the trained forelimb.…”