title: Dalfampridine improves sensorimotor function in rats with chronic deficits after middle cerebral artery occlusion.
abstract: OBJECTIVE
  Stroke survivors often have permanent deficits that are only partially addressed by physical therapy. This study evaluated the effects of dalfampridine, a potassium channel blocker, on persistent sensorimotor deficits in rats with treatment initiated 4 or 8 weeks after stroke.
  
  
  METHODS
  Rats underwent permanent middle cerebral artery occlusion. Sensorimotor function was measured using limb-placing and body-swing symmetry tests, which normally show a partial recovery from initial deficits that plateaus ≈4 weeks after permanent middle cerebral artery occlusion. Dalfampridine was administered starting at 4 or 8 weeks after permanent middle cerebral artery occlusion in 2 blinded, vehicle-controlled studies. Plasma samples were collected and brain tissue was processed for histologic assessment.
  
  
  RESULTS
  Dalfampridine treatment (0.5-2.0 mg/kg) improved forelimb- and hindlimb-placing responses and body-swing symmetry in a reversible and dose-dependent manner. Plasma dalfampridine concentrations correlated with dose. Brain infarct volumes showed no differences between treatment groups.
  
  
  CONCLUSIONS
  Dalfampridine improves sensorimotor function in the rat permanent middle cerebral artery occlusion model. Dalfampridine extended-release tablets (prolonged release fampridine outside the United States) are used to improve walking in patients with multiple sclerosis, and these preclinical data provide a strong rationale for examining the potential of dalfampridine to treat chronic stable deficits in stroke patients.
  
  
  BACKGROUND
  http://www.clinicaltrials.gov. Unique identifier: NCT01605825.
authors: Acorda Therapeutics, Inc, Ardsley, NY, USA. jiaci@acorda.com
authors: Jennifer F
authors: JF
authors: Iaci
authors: Tom J
authors: TJ
authors: Parry
authors: Zhihong
authors: Z
authors: Huang
authors: Seth P
authors: SP
authors: Finklestein
authors: Jingmei
authors: J
authors: Ren
authors: Dana K
authors: DK
authors: Barrile
authors: Matthew D
authors: MD
authors: Davenport
authors: Rui
authors: R
authors: Wu
authors: Andrew R
authors: AR
authors: Blight
authors: Anthony O
authors: AO
authors: Caggiano
mesh_terms: D015761:4-Aminopyridine / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D018592:Cross-Over Studies; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D020244:Infarction, Middle Cerebral Artery / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D026902:Potassium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D011597:Psychomotor Performance / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D026902:Potassium Channel Blockers; D015761:4-Aminopyridine
keywords: 4-aminopyridine; chronic ischemia; demyelination; ischemic stroke; recovery