• Syoichi Tashiro, Munehisa Shinozaki, Masahiko Mukaino, François Renault-Mihara, Yoshiaki Toyama, Meigen Liu, Masaya Nakamura, and Hideyuki Okano.
• Department of Rehabilitation Medicine, Keio University School of Medicine, Tokyo, Japan.
• Neurorehabil Neural Repair. 2015 Aug 1; 29 (7): 677-89.

BackgroundSpasticity and allodynia are major sequelae that affect the quality of life and daily activities of spinal cord injury (SCI) patients. Although rehabilitation ameliorates spasticity and allodynia, the molecular mechanisms involved in these processes remain elusive.ObjectiveTo investigate the molecular mechanisms by which rehabilitation ameliorates spasticity and allodynia after SCI in rats.MethodsThe expression levels of brain-derived neurotrophic factor (BDNF) and potassium-chloride cotransporter-2 (KCC2), as well as the localization of KCC2, were examined in the lumbar enlargements of untrained and treadmill-trained thoracic SCI model rats. Spasticity and allodynia were determined via behavioral and electrophysiological analyses. The effects of BDNF on spasticity, allodynia, and KCC2 activation were determined by inhibition of BDNF signaling via intrathecal administration of TrkB-IgG. The effects of SCI and training on the expression levels of functional phospholipase C-γ in the lumbar enlargement were also examined.ResultsTreadmill training after SCI upregulated endogenous BDNF expression and posttranslational modification of KCC2 in the lumbar enlargement significantly. There were also significant correlations between increased KCC2 expression and ameliorated spasticity and allodynia. Administration of TrkB-IgG abrogated the training-induced upregulation of KCC2 and beneficial effects on spasticity and allodynia. The expression level of functional phospholipase C-γ was reduced significantly after SCI, which may have contributed to the change in the function of BDNF, whereby it did not trigger short-term downregulation or induce long-term upregulation of KCC2 expression secondary to training.ConclusionsBDNF-mediated restoration of KCC2 expression underlies the suppression of spasticity and allodynia caused by rehabilitation.© The Author(s) 2014.

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