Constraint-Induced Movement Therapy Enhanced Neurogenesis and Behavioral Recovery after Stroke in Adult Rats

Department of Neurology, The First Affiliated Hospital, China Medical University.
The Tohoku Journal of Experimental Medicine (Impact Factor: 1.28). 08/2009; 218(4):301-8. DOI: 10.1620/tjem.218.301
Source: PubMed

ABSTRACT Constraint-induced movement therapy (CIMT) has been extensively used for stroke rehabilitation. CIMT encourages use of the impaired limb along with restraint of the ipsilesional limb in daily life, and may promote behavioral recovery and induce structural changes in brain after stroke. The aim of this study was to investigate whether CIMT enhances neurogenesis in rat brain after stroke that was generated by middle cerebral artery occlusion. Adult rats were divided into sham group, ischemia group and ischemia treated with CIMT group. Rats of CIMT group were treated with a plaster cast to restrain the healthy forelimb for 14 days beginning 1 week after ischemia. The proliferation of neuronal cells labeled with bromodeoxyuridine (BrdU) and behavioral recovery were analyzed at day 29 after ischemia. We also measured the tissue level of stromal cell-derived factor 1 (SDF-1) by ELISA. SDF-1 might be involved in the regulation of neurogenesis following stroke. In the subventricular zone of the animals treated with CIMT, there was a significant increase in the number of BrdU-positive cells (135 +/- 18, P < 0.05), compared with ischemia group (87 +/- 12) or sham group (18 +/- 3.6). Likewise, in the dentate gyrus, animals treated with CIMT showed a significant increase in BrdU-positive cells (296 +/- 26, P < 0.05) compared with ischemia group (225 +/- 18) or sham group (162 +/- 11). CIMT treatment after stroke significantly improved behavioral performances and increased the SDF-1 protein levels in the cortex and dentate gyrus. In conclusion, CIMT treatment enhances neurogenesis and functional recovery after stroke.

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    • "The latter has particular basic significance because the effectiveness of CI therapy has been linked to neuroplasticity, a process that could theoretically be constrained by inflammatory response in surviving damaged tissue (Hughes et al., 2010; Jin et al., 2014; Price et al., 2006). Prior work shows that CI therapy has the potential to alter brain structure (Gauthier et al., 2008; Sterling et al., 2013), cortical excitability (Liepert et al., 2000), neurogenesis and gene expression (in animal models) (Maier et al., 2008; Schneider et al., 2014; Zhao et al., 2009). Moreover, grey matter density in nondamaged regions has been shown to predict CI therapy response (Gauthier et al., 2012). "
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    ABSTRACT: Purpose: The purpose of this study was to delineate the relationship between several types of T1-weighted MRI pathology and motor rehabilitation potential following Constraint Induced Movement therapy (CI therapy) in chronic stroke. Methods: Stepwise regression was employed (n = 80) to identify predictors of motor recovery (prior to therapy) and of response to Constraint-Induced Movement therapy [measured via the Wolf Motor Function Test (WMFT) and Motor Activity Log (MAL)] from among the following: age, side of motor deficit, chronicity, gender, lesion volume, peri-infarct damage volume, white matter hypointensity volume, ventricular asymmetry, and lesion location. Results: Although extent of total stroke damage weakly correlated with poorer performance on the WMFT prior to therapy, this relationship was mediated by the location of the damage. No metric of tissue damage examined here was associated with real-world arm use at baseline (MAL at pre-treatment) or with CI therapy-induced improvement in either best motor performance upon request (WMFT) or spontaneous arm use for daily activities (MAL). Conclusions: In sum, the extent of brain tissue damage of any type examined here poorly predicted motor function and response to rehabilitation in chronic stroke.
    Restorative neurology and neuroscience 09/2014; DOI:10.3233/RNN-130366 · 4.18 Impact Factor
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    • "Our results are consistent with several previous experimental (Allred et al., 2010; Rha et al., 2011; Zhao et al., 2009) and clinical (Boggio et al., 2007; Bradnam et al., 2011; Kang et al., 2011; Nair et al., 2011) studies, in which attenuating the effect of the contralesional hemisphere improved functional motor recovery after brain infarction. However, other experimental (Jin et al., 2011; Napieralski et al., 1998; Shanina et al., 2006) and clinical (Takeuchi et al., 2012) stroke studies have yielded opposite conclusions. "
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    ABSTRACT: Purpose: Clinical studies suggest a correlation between changes in activity of the contralesional cerebral cortex and spontaneous recovery from stroke, but whether this is a causal relationship is uncertain. Methods: Young adult Sprague-Dawley male rats underwent unilateral or bilateral permanent distal middle cerebral artery occlusion (dMCAO). Infarct volume was determined by 2,3,5-triphenyltetrazolium chloride (TTC) staining 24 hr after dMCAO, and functional outcome was assessed 1-28 days after dMCAO using the ladder rung walking and limb placing tests. Results: Infarct volume was unchanged, but functional neurological deficits were reduced 1 day after bilateral compared to unilateral dMCAO. Conclusions: Activity in the contralesional cerebral cortex may inhibit functional motor recovery after experimental stroke.
    Restorative neurology and neuroscience 08/2012; 30(6). DOI:10.3233/RNN-2012-120254 · 4.18 Impact Factor
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    • "Further , the effects of CIT on a molecular level in adult rats with stroke were under evaluation. Compared with the control group, the ischemia group with CIT treatment showed improvement in neurogenesis and expression of stromal cellderived factor-1 (SDF-1), a cytokine involved in proliferation and differentiation of neural progenitor/stem cells [60]. Although investigations of neuronal change on molecular and cellular level are scarce, these studies provided the evidence to support that behavioral improvement is based on neuronal regeneration involving neurogenesis, synapse formation, and upregulation of neurotrophic factors. "
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    ABSTRACT: There is an increasing awareness about the importance of translation from basic scientific findings into practical application for efficiently improving human health, especially in the pharmaceutical industry. In the field of neurorehabilitation, however, the bench-to-bedside process continues to be developing, and thus most of the therapeutic interventions have encountered barriers during exploration of evidence-based effectiveness. Despite this immaturity, constraint-induced movement therapy (CIT), a well-evidenced treatment evolved from research in nonhuman primates, is suggested to be an ideal paradigm of translational research in the field of neurorehabilitation. This article reviews the evolvement of CIT with regards to its behavioral efficacy and neuroimaging evidence through the translation roadmap developed by the National Institutes of Health. We also discuss prospects for the application of combined interventions, such as stem cell therapy or pharmaceutical prescription, with appropriate screening of patients beforehand, as well as an efficient delivery mode after the treatment. To achieve such goals and consolidate evidenced-based neurorehabilitation, we provide a framework for applications into the translational research of other therapeutic interventions aside from CIT.
    American Journal of Translational Research 01/2010; 3(1):48-60. · 3.23 Impact Factor
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