Abstract 162: Vagus Nerve Stimulation Enhances Neuroplasticity and Forelimb Recovery after Stroke in Aged Rats
Background: Advanced age is a leading risk factor for stroke and is associated with worse recovery. The goal of post-stroke rehabilitative therapies is to enhance neuroplasticity to support the recovery of motor function. Recent studies indicate that vagus nerve stimulation (VNS) paired with rehabilitative training drives robust plasticity and results in significantly enhanced recovery of forelimb function in multiple models of brain injury in young rats. Advanced age may interfere with the benefits of VNS by reducing the capacity for plasticity. Here were evaluate the ability of VNS to drive neuroplasticity and improve forelimb recovery after stroke in aged subjects, and we examine mechanisms that may underlie recovery.
Methods: In the first set of experiments, aged (16 mo. old) rats performed an automated forelimb task and then were trained for 5 days with (n = 2) or without VNS (n = 2) paired with forelimb movement. Movement representations were then assayed using ICMS. In the second set of experiments, aged rats were trained on the isometric force task and then received a cortical ischemic lesion and VNS cuff electrode. Rats underwent 6 weeks of rehabilitative training with (n = 8) or without paired VNS (n = 9). At the end of testing, rats received an injection of biotinylated dextran amine into the contralesional motor cortex to label corticospinal tract (CST) projections from the unlesioned hemisphere.
Results: Early findings suggest that VNS paired with motor training results in a 244 ± 104% increase in forelimb representation compared to training alone in the motor cortex of aged rats. After stroke, VNS paired with rehabilitative results in significantly enhanced motor recovery compared to extensive rehabilitative training without VNS in aged rats. Rats that receive VNS+Rehab display 100 ± 7% recovery of forelimb strength compared to a 56 ± 14% recovery in rats that receive Rehab alone. Preliminary results indicate that VNS promotes increased connectivity of the CST from the unlesioned hemisphere to the denervated side of the spinal cord.
Conclusions: VNS significantly enhances neuroplasticity and post-stroke recovery in aged rats. The VNS-dependent increase in recovery may be supported by reorganization of CST projections from the unlesioned motor cortex.
Author Disclosures: S.A. Hays: None. A. Ruiz: None. D.R. Hulsey: None. N. Khodaparast: None. T. Bethea: None. J.B. Carmel: None. R.L. Rennaker: Ownership Interest; Significant; Vulintus, LLC. M.P. Kilgard: Consultant/Advisory Board; Modest; MicroTransponder, Inc..
- © 2015 by American Heart Association, Inc.