Constraint-Induced Movement Therapy and Rehabilitation Exercises Lessen Motor Deficits and Volume of Brain Injury After Striatal Hemorrhagic Stroke in Rats

Abstract

Background and Purpose-Constraint-induced movement therapy (CIMT) promotes motor recovery after occlusive stroke in humans, but its efficacy after intracerebral hemorrhage (ICH) has not been investigated clinically or in the laboratory. In this study we tested whether CIMT and a rehabilitation exercise program would lessen motor deficits after ICH in rats. Methods-Rats were subjected to striatal ICH (via infusion of collagenase) or sham stroke. Seven days later, treatment began with CIMT (8 h/d of ipsilateral forelimb restraint), rehabilitation exercises (eg, reaching, walking; 1 h/d), or both for 7 days. Some rats were not treated. Motor deficits were assessed up to the 60-day survival time, after which the volume of tissue lost was determined. Results-Untreated ICH rats made more limb slips traversing a horizontal ladder and showed an asymmetry toward less use of the contralateral paw in the cylinder test of limb use asymmetry (day 28). These rats were also significantly less successful in the Montoya staircase test (days 55 to 59) of skilled reaching. Neither therapy alone provided much benefit. However, the combination of daily exercises and CIMT substantially and persistently improved recovery. Unexpectedly, this group had a statistically smaller volume of tissue lost than untreated ICH rats. Conclusions-The combination of focused rehabilitation exercises and CIMT effectively promotes functional recovery after ICH, while either therapy alone is less effective. This therapy may work in part by reducing the volume of tissue lost, likely through reducing atrophy while promoting remodeling.

MMP-9 Deficiency Enhances Collagenase-Induced Intracerebral Hemorrhage and Brain Injury in Mutant Mice

“…Even though collagenase does not discriminate among different brain tissues, it produces massive bleeding and mortality, similar to that in human ICH. This model has been used extensively in investigations of ICH (Brown et al, 1995;DeBow et al, 2003;Del Bigio et al, 1996;Elger et al, 1994;Lyden et al, 1997;MacLellan et al, 2002;Matsushita et al, 2000;Rosenberg and Navratil, 1997;Rosenberg et al, 1992), including studies on the long-term deficits after collagenase-induced ICH (Chesney et al, 1995). Another animal model used to determine ICH pathophysiology and to evaluate therapeutic treatment (Andaluz et al, 2002) is the direct injection of autologous blood into the rat caudate nucleus (Nath et al, 1986), a model used in numerous studies (Bullock et al, 1984;Huang et al, 2002;Jiang et al, 2002;Mendelow, 1993;Nath et al, 1987;Thulborn et al, 1990;Xue and Del Bigio, 2000;Wu et al, 2002).…”

A novel approach to induction and rehabilitation of deficits in forelimb function in a rat model of ischemic stroke

“…Acta Pharmacologica Sinica npg limb, functional recovery could be promoted [7] . Moreover, exposure of rats to task-specific [7,31,32] or nonspecific [10,[33][34][35][36] forelimb activity post-ischemia can improve functional outcomes.…”

“…Moreover, exposure of rats to task-specific [7,31,32] or nonspecific [10,[33][34][35][36] forelimb activity post-ischemia can improve functional outcomes. Notably, some experimental models of forced limb use in rodents have resulted in increased damage and worsened functional recovery [8,[37][38][39] .…”

“…Previous attempts to model CIMT in rodents have resulted in discrepant results [7][8][9][10] , probably due to a combination of the varied stroke models used and confounding effects of stress when forelimb function is constrained in rodents. Models of middle cerebral artery occlusion (MCAo), in which the MCA is exposed and occluded permanently or temporarily have conventionally been used to study post-ischemic sensorimotor impairment.…”

Brain-dependent movements and cerebral-spinal connections: Key targets of cellular and behavioral enrichment in CNS injury models

“…It is reasonable to expect that secondary degeneration of neurons might be attenuated by intense behavioral demand if the early vulnerable period is avoided. Indeed, a recent report of rats sustaining striatal hemorrhage indicated that a daily regimen of exercise, alternating with intermittent immobilization of the nonimpaired forelimb beginning 8 days after the initial insult, rescued neurons from delayed chronic degeneration [47]. It is very difficult to know, without unbiased stereological analysis of many regions of the brain at multiple time points, whether a motor treatment is optimally beneficial.…”