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: 1.35). 08/2009; 218(4):301-8. DOI: 10.1620/tjem.218.301
Source: PubMed


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; 32(6). DOI:10.3233/RNN-130366 · 2.49 Impact Factor
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    • "In contrast, specific rehabilitative training of the impaired forelimb (skilled reaching training) is able to increase dentate neurogenesis relative to nontrained stroke rats, although at lower levels when compared with sham-operated animals. Moreover, increased levels of newborn granule cells generated in the dentate gyrus correlate with better functional outcomes [181, 182]. "
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    ABSTRACT: Stroke is a common and disabling global health-care problem, which is the third most common cause of death and one of the main causes of acquired adult disability in many countries. Rehabilitation interventions are a major component of patient care. In the last few years, brain stimulation, mirror therapy, action observation, or mental practice with motor imagery has emerged as interesting options as add-on interventions to standard physical therapies. The neural bases for poststroke recovery rely on the concept of plasticity, namely, the ability of central nervous system cells to modify their structure and function in response to external stimuli. In this review, we will discuss recent noninvasive strategies employed to enhance functional recovery in stroke patients and we will provide an overview of neural plastic events associated with rehabilitation in preclinical models of stroke.
    Neural Plasticity 06/2013; 2013(12):854597. DOI:10.1155/2013/854597 · 3.58 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 · 2.49 Impact Factor
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