title: A novel approach to induction and rehabilitation of deficits in forelimb function in a rat model of ischemic stroke.
abstract: OBJECTIVE
  Constraint-induced movement therapy (CIMT), which forces use of the impaired arm following unilateral stroke, promotes functional recovery in the clinic but animal models of CIMT have yielded mixed results. The aim of this study is to develop a refined endothelin-1 (ET-1) model of focal ischemic injury in rats that resulted in reproducible, well-defined lesions and reliable upper extremity impairments, and to determine if an appetitively motivated form of rehabilitation (voluntary forced use movement therapy; FUMT) would accelerate post-ischemic motor recovery.
  
  
  METHODS
  Male Sprague Dawley rats (3 months old) were given multiple intracerebral microinjections of ET-1 into the sensorimotor cortex and dorsolateral striatum. Sham-operated rats received the same surgical procedure up to but not including the drill holes on the skull. Functional deficits were assessed using two tests of forelimb placing, a forelimb postural reflex test, a forelimb asymmetry test, and a horizontal ladder test. In a separate experiment ET-1 stroke rats were subjected to daily rehabilitation with FUMT or with a control therapy beginning on post-surgery d 5. Performance and post-mortem analysis of lesion volume and regional BDNF expression were measured.
  
  
  RESULTS
  Following microinjections of ET-1 animals exhibited significant deficits in contralateral forelimb function on a variety of tests compared with the sham group. These deficits persisted for up to 20 d with no mortality and were associated with consistent lesion volumes. FUMT therapy resulted in a modest but significantly accelerated recovery in the forelimb function as compared with the control therapy, but did not affect lesion size or BDNF expression in the ipsilesional hemisphere.
  
  
  CONCLUSIONS
  We conclude that refined ET-1 microinjection protocols and forcing use of the impaired forelimb in an appetitively motivated paradigm may prove useful in developing strategies to study post-ischemic rehabilitation and neuroplasticity.
authors.affiliation: Department of Biomedical Sciences, University of Prince Edward Island, Charlottetown, PE, Canada.
authors.forename: Jessica Mary
authors.initials: JM
authors.lastname: Livingston-Thomas
authors.forename: Andrew Wilson
authors.initials: AW
authors.lastname: Hume
authors.forename: Tracy Ann
authors.initials: TA
authors.lastname: Doucette
authors.forename: Richard Andrew
authors.initials: RA
authors.lastname: Tasker
mesh_terms: D000818:Animals; D001921:Brain / Q000503:physiopathology*; D002545:Brain Ischemia / Q000139:chemically induced / Q000503:physiopathology* / Q000534:rehabilitation*; D019208:Brain-Derived Neurotrophic Factor / Q000032:analysis; D019332:Endothelin-1; D005552:Forelimb / Q000503:physiopathology*; D008297:Male; D026741:Physical Therapy Modalities; D011597:Psychomotor Performance; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D019332:Endothelin-1