Vagus nerve stimulation during rehabilitative training improves functional recovery after intracerebral hemorrhage

Abstract

Background and purpose: Vagus nerve stimulation (VNS) delivered during rehabilitative training enhances neuroplasticity and improves recovery in models of cortical ischemic stroke. However, VNS therapy has not been applied in a model of subcortical intracerebral hemorrhage (ICH). We hypothesized that VNS paired with rehabilitative training after ICH would enhance recovery of forelimb motor function beyond rehabilitative training alone.

Methods: Rats were trained to perform an automated, quantitative measure of forelimb function. Once proficient, rats received an intrastriatal injection of bacterial collagenase to induce ICH. Rats then underwent VNS paired with rehabilitative training (VNS+Rehab; n=14) or rehabilitative training without VNS (Rehab; n=12). Rehabilitative training began ≥9 days after ICH and continued for 6 weeks.

Results: VNS paired with rehabilitative training significantly improved recovery of forelimb function when compared with rehabilitative training without VNS. The VNS+Rehab group displayed a 77% recovery of function, whereas the Rehab group only exhibited 29% recovery. Recovery was sustained after cessation of stimulation. Both groups performed similar amounts of trials during rehabilitative, and lesion size was not different between groups.

Conclusions: VNS paired with rehabilitative training confers significantly improved forelimb recovery after ICH compared to rehabilitative training without VNS.

Keywords: cerebral hemorrhage; rehabilitation; vagal nerve stimulation; vagus nerve.

Conflict of interest statement

Disclosures:

MPK is a consultant and has a financial interest in MicroTransponder, Inc. AMS is an employee of, and RLR owns, Vulintus, Inc. Other authors declare no conflicts of interest.

© 2014 American Heart Association, Inc.

Figures

Fig. 1

VNS paired with rehabilitative training improves forelimb recovery after ICH. (A) VNS paired with rehabilitative training (N = 14) improves hit rate by the second week of therapy compared to rehabilitative training without VNS (N = 12). Recovery is maintained after the cessation of VNS on week six. (B) VNS paired with rehabilitative training improves second press latency compared to rehabilitative training without VNS. (C) The number of trials performed by the Rehab and VNS+Rehab groups is not different at any time point during testing. * denotes P < 0.05 between Rehab and VNS+Rehab group at each time point.

Fig. 2

Lesion size is not affected by VNS. Representative images showing ICH lesions from a subject in the Rehab group (A) and the VNS+Rehab group (B). (C) No difference was observed in tissue loss between groups.