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The timing and amount of vagus nerve stimulation during rehabilitative training affect poststroke recovery of forelimb strength

Hays, Seth A.a,b; Khodaparast, Navida,b; Ruiz, Andreaa,b; Sloan, Andrew M.a,b; Hulsey, Daniel R.a,b; Rennaker, Robert L. IIa,b,c; Kilgard, Michael P.a,b

doi: 10.1097/WNR.0000000000000154

Loss of upper arm strength after stroke is a leading cause of disability. Strategies that can enhance the benefits of rehabilitative training could improve motor function after stroke. Recent studies in a rat model of ischemic stroke have demonstrated that vagus nerve stimulation (VNS) paired with rehabilitative training substantially improves recovery of forelimb strength compared with extensive rehabilitative training without VNS. Here we report that the timing and amount of stimulation affect the degree of forelimb strength recovery. Similar amounts of Delayed VNS delivered 2 h after daily rehabilitative training sessions resulted in significantly less improvement compared with that on delivery of VNS that is paired with identical rehabilitative training. Significantly less recovery also occurred when several-fold more VNS was delivered during rehabilitative training. Both delayed and additional VNS confer moderately improved recovery compared with extensive rehabilitative training without VNS, but fail to enhance recovery to the same degree as VNS that is timed to occur with successful movements. These findings confirm that VNS paired with rehabilitative training holds promise for restoring forelimb strength poststroke and indicate that both the timing and the amount of VNS should be optimized to maximize therapeutic benefits.

aDepartment of Neuroscience, School of Behavioral Brain Sciences

bTexas Biomedical Device Center

cDepartment of Bioengineering, Erik Jonsson School of Engineering and Computer Science, The University of Texas at Dallas, Richardson, Texas, USA

Correspondence to Seth A. Hays, PhD, School of Behavioral Brain Sciences, The University of Texas at Dallas, 800 West Campbell Road, GR41, Richardson, TX 75080-3021, USA Tel: +1 972 883 2376; fax: +1 972 883 2491; e-mail:

Received December 13, 2013

Accepted February 26, 2014

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