title: Combination of early constraint-induced movement therapy and fasudil enhances motor recovery after ischemic stroke in rats.
abstract: OBJECTIVE
  Constraint-induced movement therapy (CIMT) is a promising technique for the recovery of upper extremity movement in chronic stroke patients. However, the effectiveness of its use in acute ischemia has not been confirmed. Myelin-associated inhibitors, which have upregulated functions in tissues affected by acute focal infarction, limit axonal regeneration via activation of the Rho-Rho-associated protein kinase (ROCK) pathway. The present study examined whether early CIMT combined with the ROCK inhibitor fasudil promotes motor recovery after acute ischemic stroke.
  
  
  METHODS
  Rats were trained to perform the skilled-reach test and then subjected to middle cerebral artery occlusion (MCAO), producing a stroke affecting the preferred forelimb. Rats were assigned to one of four groups (N = 6/group): (nontreated) Control, CIMT, Fasudil, or CIMT+fasudil. CIMT and/or intraperitoneal infusion of fasudil were initiated 1 day postMCAO. Skilled reach and foot fault test data were collected once before and repeatedly over 4 weeks after the operation. Infarct volumes were calculated.
  
  
  RESULTS
  All four groups showed similar forelimb impairment before treatment. The performance of CIMT alone group was similar to that of controls on both tests. Fasudil alone facilitated recovery in the foot-fault test, but not in the skilled-reach test. Rats in the CIMT+fasudil group demonstrated enhanced recovery in both tests, including better performance over time than the Fasudil group on the foot-fault test. Infarct size did not differ significantly between the groups.
  
  
  CONCLUSIONS
  Early CIMT promotes motor recovery after acute ischemic stroke when it is administered with fasudil pharmacotherapy, but not without it.
authors.affiliation: a 1 Department of Neurology.
authors.forename: Yun-hai
authors.initials: YH
authors.lastname: Liu
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: d 4 Department of Neurology & Institute of Translational Medicine at University of South China, the First People's Hospital of Chenzhou, Chenzhou, Hunan, P. R. China.
authors.forename: Feng-zhen
authors.initials: FZ
authors.lastname: Huang
authors.affiliation: a 1 Department of Neurology.
authors.forename: Yun-hong
authors.initials: YH
authors.lastname: Chen
authors.affiliation: b 2 Rehabilitation, Xiangya Hospital, Central South University, Changsha, P. R. China.
authors.forename: Hong-xing
authors.initials: HX
authors.lastname: Wang
authors.affiliation: b 2 Rehabilitation, Xiangya Hospital, Central South University, Changsha, P. R. China.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Bonney
authors.affiliation: b 2 Rehabilitation, Xiangya Hospital, Central South University, Changsha, P. R. China.
authors.forename: Bao-qiong
authors.initials: BQ
authors.lastname: Liu
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000704:Analysis of Variance; D000818:Animals; D020520:Brain Infarction / Q000188:drug therapy / Q000209:etiology; D002545:Brain Ischemia / Q000150:complications; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005081:Exercise Therapy / Q000379:methods*; D005247:Feeding Behavior / Q000187:drug effects; D008297:Male; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects*; D020521:Stroke / Q000209:etiology / Q000628:therapy*; D013997:Time Factors
chemical_list: D002121:Calcium Channel Blockers; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C049347:fasudil
keywords: Constraint-induced movement therapy (CIMT); fasudil; ischemic stroke