title: Constraint-induced movement therapy overcomes the intrinsic axonal growth-inhibitory signals in stroke rats.
abstract: OBJECTIVE
  Constraint-induced movement therapy (CIMT) improves functional outcome in patients with stroke possibly through structural plasticity. We hypothesized that CIMT could enhance axonal growth by overcoming the intrinsic growth-inhibitory signals, leading eventually to improved behavioral performance in stroke rats.
  
  
  METHODS
  Focal cerebral ischemia was induced by intracerebral injection of endothelin-1. Adult Wistar rats were divided into a sham-operated group, an ischemic group, and an ischemic group treated with CIMT. CIMT started at postoperative day 7 and continued for 3 weeks. Biotinylated dextran amine was injected into the contralateral sensorimotor cortex at postoperative day 14 to trace crossing axons at the cervical spinal cord. The expressions of Nogo-A, Nogo receptor, RhoA, and Rho-associated kinase in the peri-infarct cortex, and the expressions of biotinylated dextran amine, growth associated protein-43, synaptophysin, vGlut1, and postsynaptic density-95 in the denervated spinal cord were measured by immunohistochemistry and Western blots. Behavioral recovery was analyzed at postoperative days 29 to 32.
  
  
  RESULTS
  Infarct volumes were not different between groups after stroke. CIMT significantly increased the length and the number of midline crossings of contralateral corticospinal axons to the denervated cervical spinal cord. CIMT significantly decreased the expressions of Nogo-A/Nogo receptor and RhoA/Rho-associated kinase in the peri-infarct cortex, and increased the expressions of growth associated protein-43, synaptophysin, vGlut1, and postsynaptic density-95 in the denervated cervical spinal cord. Behavioral performances assessed by the beam-walking test and the water maze test were improved significantly by CIMT.
  
  
  CONCLUSIONS
  CIMT promoted poststroke synaptic plasticity and axonal growth at least partially by overcoming the intrinsic growth-inhibitory signaling, leading to improved behavioral outcome.
authors: Department of Neurology, The First Hospital of China Medical University, Shenyang, Liaoning, PR China.
authors: Shanshan
authors: S
authors: Zhao
authors: Mei
authors: M
authors: Zhao
authors: Ting
authors: T
authors: Xiao
authors: Jukka
authors: J
authors: Jolkkonen
authors: Chuansheng
authors: C
authors: Zhao
mesh_terms: D000818:Animals; D001369:Axons / Q000473:pathology / Q000502:physiology*; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000009:adverse effects; D019922:GAP-43 Protein / Q000378:metabolism; D058851:GPI-Linked Proteins / Q000378:metabolism; D007276:Injections, Intraventricular; D008297:Male; D009068:Movement; D009185:Myelin Proteins / Q000378:metabolism; D009473:Neuronal Plasticity / Q000502:physiology; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; D026741:Physical Therapy Modalities; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000378:metabolism; D012149:Restraint, Physical; D015398:Signal Transduction / Q000502:physiology*; D020521:Stroke / Q000139:chemically induced / Q000503:physiopathology* / Q000628:therapy*; D016708:Synaptophysin / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D019332:Endothelin-1; D019922:GAP-43 Protein; D058851:GPI-Linked Proteins; D009185:Myelin Proteins; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; D011956:Receptors, Cell Surface; C000603197:Rtn4 protein, rat; C486581:Rtn4r protein, rat; D016708:Synaptophysin; D020742:rhoA GTP-Binding Protein
keywords: axonal growth; constraint-induced movement therapy; functional recovery; stroke