title: Forced limb-use enhances brain plasticity through the cAMP/PKA/CREB signal transduction pathway after stroke in adult rats.
abstract: OBJECTIVE
  The mechanism underlying forced limb-use -induced structural plasticity remains to be studied. We examined whether the cyclic adenosine monophosphate (cAMP)-mediated signal transduction pathway was involved in brain plasticity and promoted behavioral recovery induced by forced limb-use after stroke.
  
  
  METHODS
  Adult rats were divided into a sham group, an ischemia group, an ischemia group with forced limb-use, and an ischemia group with forced limb-use and infusion of N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinoline-sulfonamide (H89). Forced limb-use began on post-stroke day 7. Biotinylated dextran amine (BDA) was injected into the sensorimotor cortex on post-stroke day 14. Behavioral recovery was evaluated on post-stroke days 29 to 32, and the levels of cAMP, PKA C-α, phosphorylated CREB (pCREB), synaptophysin, PSD-95, BDA, and BrdU/NeuN were measured.
  
  
  RESULTS
  The number of midline-crossing axons and the expression levels of synaptophysin and PSD-95 were increased after forced limb-use. Forced limb-use enhanced the survival of the newborn neurons and increased the levels of cAMP, PKA C-α and pCREB. These were significantly suppressed by H89. Behavioral performance improved with forced limb-use and was reversed with H89.
  
  
  CONCLUSIONS
  Enhanced structural plasticity and the behavioral recovery promoted by post-stroke forced limb-use are suggested to be mediated through the cAMP/PKA/CREB signal transduction pathway.
authors.affiliation: Neurology, The First Hospital of China Medical University, Shenyang, China.
authors.forename: Huiling
authors.initials: H
authors.lastname: Qu
authors.affiliation: Cardiology, Shengjing Hospital of China Medical University, Shenyang, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Neurology, The First Hospital of China Medical University, Shenyang, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Dermatology, The First Hospital of China Medical University, Shenyang, China Key Laboratory of Immunodermatology, Ministry of Health, Ministry of Education, Shenyang, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Xiao
authors.affiliation: Biology, Lycoming College, Williamsport, PA, USA.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Tang
authors.affiliation: Biology, Lycoming College, Williamsport, PA, USA.
authors.forename: Dongjiao
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Institute of Clinical Medicine - Neurology, University of Eastern Finland, Kuopio, Finland.
authors.forename: Jukka
authors.initials: J
authors.lastname: Jolkkonen
authors.affiliation: Neurology, The First Hospital of China Medical University, Shenyang, China.
authors.forename: Chuansheng
authors.initials: C
authors.lastname: Zhao
mesh_terms: D000818:Animals; D001710:Biotin / Q000031:analogs & derivatives; D001921:Brain / Q000503:physiopathology*; D050882:CREB-Binding Protein / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D003911:Dextrans; D004195:Disease Models, Animal; D000076122:Disks Large Homolog 4 Protein; D019332:Endothelin-1; D005121:Extremities / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007546:Isoquinolines / Q000494:pharmacology; D008124:Locomotion / Q000187:drug effects; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D009473:Neuronal Plasticity / Q000502:physiology*; D051571:Protein Kinase C-alpha / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012149:Restraint, Physical / Q000379:methods*; D020521:Stroke / Q000139:chemically induced; D000071939:Stroke Rehabilitation; D013449:Sulfonamides / Q000494:pharmacology; D016708:Synaptophysin / Q000378:metabolism
chemical_list: D003911:Dextrans; D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D019332:Endothelin-1; D047908:Intracellular Signaling Peptides and Proteins; D007546:Isoquinolines; D008565:Membrane Proteins; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D016708:Synaptophysin; C076397:biotinylated dextran amine; D001710:Biotin; D000242:Cyclic AMP; D050882:CREB-Binding Protein; D051571:Protein Kinase C-alpha; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide
keywords: Axonal growth; cAMP; forced limb-use; neurogenesis; stroke