title: Enduring Poststroke Motor Functional Improvements by a Well-Timed Combination of Motor Rehabilitative Training and Cortical Stimulation in Rats.
abstract: BACKGROUND
  In animal stroke models, peri-infarct cortical stimulation (CS) combined with rehabilitative reach training (RT) enhances motor functional outcome and cortical reorganization, compared with RT alone. It was unknown whether the effects of CS + RT (a) persist long after treatment, (b) can be enhanced by forcing greater use of the paretic limb, and (C) vary with treatment onset time.
  
  
  OBJECTIVE
  To test the endurance, time sensitivity, and the potential for augmentation by forced forelimb use of CS + RT treatment effects following ischemic stroke.
  
  
  METHODS
  Adult rats that were proficient in skilled reaching received unilateral ischemic motor cortical lesions. RT was delivered for 3 weeks alone or concurrently with 100-Hz cathodal epidural CS, delivered at 50% of movement thresholds. In study 1, this treatment was initiated at 14 days postinfarct, with some subgroups receiving an overlapping period of continuous constraint of the nonparetic forelimb to force use of the paretic limb. The function of the paretic limb was assessed weekly for 9 to 10 months posttreatment. In study 2, rats underwent CS, RT, and the combination during the chronic postinfarct period.
  
  
  RESULTS
  Early onset CS + RT resulted in greater functional improvements than RT alone. The CS-related gains persisted for 9 to 10 months posttreatment and were not significantly influenced by forced use of the paretic limb. When treatment onset was delayed until 3 months post-infarct, RT alone improved function, but CS + RT was no more effective than RT alone.
  
  
  CONCLUSIONS
  CS can enhance the persistence, as well as the magnitude of RT-driven functional improvements, but its effectiveness in doing so may vary with time postinfarct.
authors.affiliation: The University of Texas at Austin, Austin, TX, USA.
authors.forename: Amber J
authors.initials: AJ
authors.lastname: O'Bryant
authors.affiliation: Medical University of South Carolina, Charleston, SC, USA.
authors.forename: DeAnna L
authors.initials: DL
authors.lastname: Adkins
authors.affiliation: The University of Texas at Austin, Austin, TX, USA.
authors.forename: Austen A
authors.initials: AA
authors.lastname: Sitko
authors.affiliation: The University of Texas at Austin, Austin, TX, USA.
authors.forename: Hannah L
authors.initials: HL
authors.lastname: Combs
authors.affiliation: The University of Texas at Austin, Austin, TX, USA.
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Nordquist
authors.affiliation: The University of Texas at Austin, Austin, TX, USA tj@austin.utexas.edu.
authors.forename: Theresa A
authors.initials: TA
authors.lastname: Jones
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000150:complications; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D004599:Electric Stimulation Therapy / Q000379:methods*; D005081:Exercise Therapy / Q000379:methods*; D008297:Male; D009044:Motor Cortex / Q000503:physiopathology*; D051381:Rats; D020318:Rats, Long-Evans; D020521:Stroke / Q000209:etiology / Q000628:therapy*; D000071939:Stroke Rehabilitation; D013997:Time Factors
keywords: constraint-induced movement therapy; facilitative stimulation; ischemia; motor cortex; motor skill learning; recovery of function