Early constraint-induced movement therapy promotes functional recovery and neuronal plasticity in a subcortical hemorrhage model rat

• Published in: Behavioural brain research Vol. 284; pp. 158 - 166
• Main Authors: Ishida, Akimasa, Misumi, Sachiyo, Ueda, Yoshitomo, Shimizu, Yuko, Cha-Gyun, Jung, Tamakoshi, Keigo, Ishida, Kazuto, Hida, Hideki
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.05.2015
• Subjects: Animals; Brain-Derived Neurotrophic Factor - metabolism; Cerebral Hemorrhage - pathology; Cerebral Hemorrhage - physiopathology; Cerebral Hemorrhage - rehabilitation; Collagenases; Dendrites - pathology; Dendrites - physiology; Exercise Therapy - methods; Forelimb - physiopathology; Forelimb function; Functional Laterality - physiology; GAP-43 Protein - metabolism; Globus Pallidus; Growth factor; Intracerebral hemorrhage; Male; Motor Skills - physiology; Neuronal Plasticity - physiology; Plasticity; Proto-Oncogene Proteins c-fos - metabolism; Pyramidal Cells - pathology; Pyramidal Cells - physiology; Rat; Rats, Wistar; Recovery of Function - physiology; Rehabilitation; Sensorimotor Cortex - pathology; Sensorimotor Cortex - physiopathology; Time Factors; L-CIMT; Rat; CST; SMC; CNS; Forelimb function; E-CIMT; Intracerebral hemorrhage; ICH; CIMT; Plasticity; IC; Rehabilitation; Growth factor
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2015.02.022

•Forelimb function after subcortical hemorrhage was recovered by delivering early CIMT.•Early CIMT induced plastic changes in the ipsi-lesional sensorimotor cortex.•Late-CIMT failed to induce the plastic changes in ipsi-lesional sensorimotor cortex. Constraint-induced movement therapy (CIMT) promotes functional recovery of impaired forelimbs after hemiplegic strokes, including intracerebral hemorrhage (ICH). We used a rat model of subcortical hemorrhage to compare the effects of delivering early or late CIMT after ICH. The rat model was made by injecting collagenase into the globus pallidus near the internal capsule, and then forcing rats to use the affected forelimb for 7 days starting either 1 day (early CIMT) or 17 days (late CIMT) after the lesion. Recovery of forelimb function in the skilled reaching test and the ladder stepping test was found after early-CIMT, while no significant recovery was shown after late CIMT or in the non-CIMT controls. Early CIMT was associated with greater numbers of ΔFosB-positive cells in the ipsi-lesional sensorimotor cortex layers II–III and V. Additionally, we found expression of the growth-related genes brain-derived neurotrophic factor (BDNF) and growth-related protein 43 (GAP-43), and abundant dendritic arborization of pyramidal neurons in the sensorimotor area. Similar results were not detected in the contra-lesional cortex. In contrast to early CIMT, late CIMT failed to induce any changes in plasticity. We conclude that CIMT induces molecular and morphological plasticity in the ipsi-lesional sensorimotor cortex and facilitates better functional recovery when initiated immediately after hemorrhage.