Published online before print October 14, 2004, doi: 10.1161/01.STR.0000143236.51708.e9
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(Stroke. 2004;35:2690.)
© 2004 American Heart Association, Inc.
Articles |
Recovery and Rehabilitation in Stroke
Introduction
From the Landon Center on Aging and Department of Molecular and Integrative Physiology (R.J.N.), University of Kansas Medical Center, Kansas City, Ks; and the University of Florida Brooks Center for Rehabilitation Studies and Department of Veteran Affairs Rehabilitation Outcomes Research Center of Excellence (P.W.D.), Gainesville, Fla.
Correspondence to Dr Randolph J. Nudo, Director, Landon Center on Aging, Professor, Dept of Molecular and Integrative Physiology, Landon Center on Aging, Mail Stop 1005, KU Medical Center, 3901 Rainbow Blvd, Kansas City, KS 66160.
A large proportion of individuals who survive stroke are chronically disabled, making stroke a leading cause of serious, long-term disability. Although our society has made great strides in improving stroke awareness and survivability, until recently, the prospects for long-term improvement in sensorimotor disability and function were bleak. It is widely recognized that spontaneous recovery accounts for a significant portion of the functional improvement that occurs in the first several weeks after stroke. However, a number of new approaches, spurred by advances in the neurosciences, especially in the field of neuroplasticity, have provided hope that further improvement in function can be spurred by specific manipulations of the neural and behavioral environment.
The long-term consequences of ischemic damage on neuronal structures are beginning to unfold. An increasing number of studies in rodents, nonhuman primates, and humans have now demonstrated the potential for sensorimotor regions of the brain to undergo structural and functional alterations as a function of use and injury. After neuronal death, such as occurs in stroke, spared neural structures in the adjacent tissue, and remote structures in the ipsilesional and contralesional (intact) hemisphere undergo significant functional changes. For example, GABAa receptors are downregulated in widespread regions of the spared cerebral cortex for long periods of time after the initial infarct. Dendrites proliferate, are subsequently pruned, and substantial synaptogenesis occurs. Hemodynamic changes occur throughout the spared tissue. New blood vessels are formed, at least in the peri-infarct zone.
It is becoming clear that one of the most potent modulators of neural organization after stroke is behavioral experience. Thus, injury and use interact to shape the subsequent organization of the brain. The impaired limb is not effective and often ceases to be used for skilled behavior. The individual develops compensatory strategies, using the trunk and less-affected limb to accomplish functional tasks. In turn, these emergent behavioral skills are accompanied by use-dependent changes in spared brain structures.
The development of interventions that attempt to reverse the compensatory reliance on the less-impaired limb not only have been shown to result in adaptive reorganization in the cerebral cortex but also may invigorate recovery in the impaired limb months or years after the ischemic event. The most widely examined of these interventions is constraint-induced movement therapy that relies on constraint of the less-affected limb and intensive practice of motor skills with the more-affected limb. As Grotta et al indicate in their pilot study, scores on functional motor tasks improve, concomitant with an increase in the number of sites in the affected hemisphere whose stimulation can evoke movement in the contralateral (affected) limb. The results of this study, and others, parallel those obtained in earlier neurophysiological studies in nonhuman primates.
In a surprisingly short time, new subfields that promise to revolutionize our ability to modulate brain function and to use the intact neural structure in novel ways have burst on the scene. Electrical stimulation techniques are now relatively common in the treatment of Parkinson disease and are beginning to be investigated for improved function after stroke. Robotic devices are becoming an important tool in our examination of the effects of controlled behavioral intervention in poststroke therapy. Perhaps, most remarkably, as described by Gerhard Friehs, neural prosthetic devices, using control signals derived directly from intact neural structures, may be a reality in a few years. As with constraint-induced movement therapy, this approach gained significant impetus because of seminal studies in rodent and nonhuman primate models demonstrating that animals could modulate the output of cortical neurons to control external devices.
The ultimate goal of restoring neural tissue to its original state is likely to be unrealistic. Based on altered neural pathways after stroke and the modulating influence of altered behavior, one cannot expect to simply replace the lost tissue. However, one of the most exciting arenas in restorative neuroscience is the potential that progenitor cells can differentiate into neuronal and non-neuronal cells to adaptively influence the organization of the injured brain. Although many challenges still exist, Lindvall and Kokaia outline a roadmap for the development of stem cell therapy for stroke.
Received August 5, 2004; accepted August 5, 2004.
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