title: Vagus Nerve Stimulation During Rehabilitative Training Improves Forelimb Recovery After Chronic Ischemic Stroke in Rats.
abstract: 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 vagus nerve stimulation (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.
  
  
  
  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. Then, 6 weeks after the lesion, rats underwent rehabilitative training paired with VNS (Paired VNS; n = 10), rehabilitative training with equivalent VNS delivered 2 hours after daily rehabilitative training (Delayed VNS; n = 10), or rehabilitative training without VNS (Rehab, n = 9).
  
  
  
  VNS paired with rehabilitative training significantly improved recovery of forelimb function compared with 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.
  
  
  
  VNS paired with rehabilitative training confers significantly greater recovery of forelimb function after chronic ischemic stroke in rats.
authors.affiliation: The University of Texas at Dallas, Richardson, TX 75080-3021, USA.
authors.forename: Navid
authors.initials: N
authors.lastname: Khodaparast
authors.affiliation: The University of Texas at Dallas, Richardson, TX 75080-3021, USA.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Kilgard
authors.affiliation: Micro Transponder Inc, Dallas, TX 75204, USA.
authors.forename: Reema
authors.initials: R
authors.lastname: Casavant
authors.affiliation: The University of Texas at Dallas, Richardson, TX 75080-3021, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ruiz
authors.affiliation: The University of Texas at Dallas, Richardson, TX 75080-3021, USA.
authors.forename: Iqra
authors.initials: I
authors.lastname: Qureshi
authors.affiliation: The University of Texas at Dallas, Richardson, TX 75080-3021, USA.
authors.forename: Patrick D
authors.initials: PD
authors.lastname: Ganzer
authors.affiliation: The University of Texas at Dallas, Richardson, TX 75080-3021, USA.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Rennaker
authors.affiliation: The University of Texas at Dallas, Richardson, TX 75080-3021, USA seth.hays@utdallas.edu.
authors.forename: Seth A
authors.initials: SA
authors.lastname: Hays
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002545:Brain Ischemia / Q000150:complications; D004195:Disease Models, Animal; D005260:Female; D007537:Isometric Contraction / Q000502:physiology; D010805:Physical Conditioning, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology*; D012720:Severity of Illness Index; D020521:Stroke / Q000209:etiology / Q000628:therapy*; D000071939:Stroke Rehabilitation; D016896:Treatment Outcome; D034941:Upper Extremity / Q000503:physiopathology*; D055536:Vagus Nerve Stimulation / Q000379:methods*
keywords: ischemic stroke; recovery; rehabilitation; vagal stimulation; vagus nerve