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.

Background. Vagus nerve stimulation (VNS) paired with rehabilitation may improve upper-limb impairment and function after ischemic stroke. Objective. To report 1-year safety, feasibility, adherence, and outcome data from a home exercise program paired with VNS using long-term follow-up data from a randomized double-blind study of rehabilitation therapy paired with Active VNS (n = 8) or Control VNS (n = 9). Methods. All people were implanted with a VNS device and underwent 6 weeks in clinic therapy with Control or Active VNS followed by home exercises through day 90. Thereafter, participants and investigators were unblinded. The Control VNS group then received 6 weeks in-clinic Active VNS (Cross-VNS group). All participants then performed an individualized home exercise program with self-administered Active VNS. Data from this phase are reported here. Outcome measures were Fugl-Meyer Assessment—Upper Extremity (FMA-UE), Wolf Motor Function Test (Functional and Time), Box and Block Test, Nine-Hole Peg Test, Stroke Impact Scale, and Motor Activity Log. Results. There were no VNS treatment–related serious adverse events during the long-term therapy. Two participants discontinued prior to receiving the full crossover VNS. On average, participants performed 200 ± 63 home therapy sessions, representing device use on 57.4% of home exercise days available for each participant. Pooled analysis revealed that 1 year after randomization, the FMA-UE score increased by 9.2 points (95% CI = 4.7 to 13.7; P = .001; n = 15). Other functional measures were also improved at 1 year. Conclusions. VNS combined with rehabilitation is feasible, with good long-term adherence, and may improve arm function after ischemic stroke.

No abstract

No abstract

Background: Stroke is the leading cause of serious long-term disability. Currently, there is no effective treatment for chronic stroke patients. Neuroplasticity within motor circuitry is believed to support recovery of function after stroke. We have developed a method using vagus nerve stimulation (VNS) paired with motor training to drive robust, specific plasticity in the motor cortex. Our recent studies indicated that VNS paired with rehab training significantly enhances recovery of forelimb function after cortical ischemic stroke. To further the translation potential of our therapy, we accessed the hypothesis that delivering VNS paired with rehab may improve functional recovery in rats that demonstrated chronic forelimb impairments. Methods: All female Sprague Dawley rats were trained on the Isometric Pull Task, which quantifiably measures forelimb force generation. Rats that achieved 5 consecutive days of over 85% hit rate on this task were given a unilateral cortical-subcortical ischemic lesion via injections of a vasoconstrictive peptide, endothelin-1. Following the lesion, rats returned to their home cage, and did not begin rehab training until 5 weeks post-lesion. Upon return, post-lesion forelimb impairment was accessed with the same task parameters used during pre-lesion training, which allowed for a direct comparison of performance. Rats were assigned to balanced treatment groups based on post-lesion baseline hit rate. Treatment groups consisted of VNS delivered during rehab training (Paired VNS; n=10), VNS delivered two hours after rehab training (Delayed VNS; n=10), and rehab training without VNS (Rehab; n=10). Results: At five weeks post-lesion, the unilateral ischemic insult significantly worsened performance in all three groups compared to pre-lesion (Paired VNS: 29.8 ± 5.7%, paired t-test, P < 0.001; Delayed VNS: 24.6 ± 2.7%, P < 0.001; Rehab: 30.4 ± 4.7%, P < 0.001). Following our therapy, the Paired VNS group demonstrated significantly better performance than both control groups (Paired VNS: 81.6 ± 2.3%, P < 0.01; Delayed VNS: 53.2 ± 6.5%, P < 0.01; Rehab: 49.8 ± 6.8%, P < 0.01). Conclusion: Our results indicate that VNS paired with rehab training can further enhance recovery of forelimb function in chronically impaired rats.