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Rouiller E.M., Yu X.H., Moret V., Tempini A., Wiesendanger M., Liang F. Dexterity in adult monkeys following early lesion of the motor cortical hand area: the role of cortex adjacent to the lesion. Eur J Neurosci. 10:1998;729-740.
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The long-term effects of removal of sensorimotor cortex in infant and adult rhesus monkeys
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A rat's reach should exceed its grasp: Analysis of independent limb and digit use in the laboratory rat
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K.-P. Ossenkopp, M. Kavaliers, & P.R. Sanberg. Austin, Texas: RG Landes Company
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Whishaw I.Q., Miklyaeva E.I. A rat's reach should exceed its grasp: analysis of independent limb and digit use in the laboratory rat. Ossenkopp K.-P., Kavaliers M., Sanberg P.R. Measuring Movement and Locomotion: From Invertebrates to Humans. 1996;135-169 RG Landes Company, Austin, Texas.
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Traumatic brain injury of the forelimb and hindlimb sensorimotor areas in the rat: Physiological, histological and behavioral correlates
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Sobolosky J.S., Matthews M.A., Davidson J.F., Tabor S.L., Carey M.E. Traumatic brain injury of the forelimb and hindlimb sensorimotor areas in the rat: physiological, histological and behavioral correlates. Behav Brain Res. 79:1996;79-92.
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Napieralski J.A., Banks R.J.A., Chesselet M.-F. Motor and somatosensory deficits following uni- and bilateral lesions of the cortex induced by aspiration or thermocoagulation in the adult rat. Exp Neurol. 154:1998;80-88.
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Relationship between dendritic pruning and behavioral recovery following sensorimotor cortex lesions
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note
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Kozlowski D.A., Schallert T. Relationship between dendritic pruning and behavioral recovery following sensorimotor cortex lesions. Behav Brain Res. 97:1998;89-98. Previous studies showed that a unilateral injury to the sensorimotor cortex of rats results in increased dendritic arborization in layer V of the homotopic contralateral cortex [66]. This dendritic growth is maximal 18 days after the lesion, at a time when behavioral performance has returned to pre-lesion levels. Subsequently, dendrites are pruned back, and return to normal levels by 45 to 60 days after the lesion. Administration of the NMDA receptor antagonist MK-801 during the pruning period prevents elimination of dendritic arbors and reinstates behavioral impairments, suggesting that pruning of exuberant dendritic arbors is an important event during functional recovery. In this study, MK-801 was administered beginning at day 18 post-lesion and continued until day 30 or day 60 post-lesion. When MK-801 was administered until day 60, dendritic pruning was blocked, and forelimb deficits were chronically reinstated. When MK-801 was administered only until day 30, dendritic pruning was blocked, but forelimb deficits recovered. This result suggests that the pruning of exuberant dendritic arbors after cortical damage is not directly related to behavioral recovery. The authors suggest that behavioral recovery may be related to more specific structural events, such as changes in dendritic spines and synapses. This paper brings into question the assumption that growth of neuronal processes after cortical injury necessarily represents a behaviorally adaptive process. The relationships between neuronal growth and behavioural recovery are not always direct, so these types of correlative studies, which examine the time course of structural and behavioral phenomena, will be crucial for developing useful models of recovery.
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The effects of amphetamine on recovery of function after cortical damage in the rat depend on the behavioral requirements of the task
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Schmanke T.D., Avery R.A., Barth T.M. The effects of amphetamine on recovery of function after cortical damage in the rat depend on the behavioral requirements of the task. J Neurotrauma. 13:1996;293-307.
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Ethanol consumption following recovery from unilateral damage to the forelimb area of the sensorimotor cortex: Reinstatement of deficits and prevention of dendritic pruning
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Kozlowski D.A., Hilliard S., Schallert T. Ethanol consumption following recovery from unilateral damage to the forelimb area of the sensorimotor cortex: reinstatement of deficits and prevention of dendritic pruning. Brain Res. 763:1997;159-166.
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Goldstein L.B., Bullman S. Effects of dorsal noradrenergic bundle lesions on recovery after sensorimotor cortex injury. Pharmacol Biochem Behav. 58:1997;1151-1157.
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H.-J. Freund, B.A. Sabel, & O.W. Witte. Philadelphia: Lippincott-Raven
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Schallert T., Kozlowski D.A., Humm J.L., Cocke R.R. Use-dependent structural events in recovery of function. Freund H.-J., Sabel B.A., Witte O.W. Brain Plasticity. Advances in Neurology. 73:1997;229-238 Lippincott-Raven, Philadelphia.
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Schallert, T.1
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Mechanisms of recovery of dexterity following unilateral lesion of the sensorimotor cortex in adult monkeys
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note
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Liu Y., Rouiller E.M. Mechanisms of recovery of dexterity following unilateral lesion of the sensorimotor cortex in adult monkeys. Exp Brain Res. 128:1999;149-159. Previous studies in adult monkeys suggested that undamaged cortical tissue adjacent to a cortical injury undergoes functional reorganzation [29,44]. This study explored the role of other cortical areas in recovery. Intracortical microstimulation techniques were used to define the hand area in primary motor cortex (M1) in both hemispheres. After unilateral damage to the M1 hand area (which also affected the primary somatosensory area), the monkeys displayed a profound deficit in dexterity in the contralateral hand. Recovery of dexterous hand function occurred over a period of several months. Following recovery, the GABA agonist muscimol was injected into various motor regions to induce transient inactivation. Inactivation of the M1 hand area of the injured or intact hemisphere had no effect on performance. However, inactivation of the premotor cortex of the injured hemisphere (simultaneous inactivation of the ventral and dorsal premotor areas) resulted in rapid deterioration in motor performance within 15 minutes after muscimol injection. This paper presents the first direct demonstration that the premotor cortex plays an important role in recovery after injury to the primary motor cortex.
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Liu, Y.1
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Recovery of motor function after focal cortical injury in primates: Compensatory movement patterns used during rehabilitative training
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Friel K.M., Nudo R.J. Recovery of motor function after focal cortical injury in primates: compensatory movement patterns used during rehabilitative training. Somatosens Mot Res. 15:1998;173-189.
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Utilization of the Denny-Brown collection: Differential recovery of forelimb and hind limb stepping after extensive unilateral cerebral lesions
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Vilensky J.A., Gilman S., Dunn E.A., Wilson W.J. Utilization of the Denny-Brown collection: differential recovery of forelimb and hind limb stepping after extensive unilateral cerebral lesions. Behav Brain Res. 82:1997;223-233.
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Kubota K. Motor cortical muscimol injection disrupts forelimb movement in freely moving monkeys. Neuroreport. 7:1996;2379-2384.
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A agonist muscimol were used to examine the effect of reversibly inactivating portions of the M1 hand area in monkeys. While the results are not directly related to recovery of function, they are highly relevant to our understanding of the behavioral effects of cortical injury in M1. The reversible lesions were focal, affecting only a portion of the M1 hand area. Such limited lesions are in contrast to the large lesions employed in most historical accounts of the effects of injury to M1, and provide key information regarding the distributed organization of motor representations. The results suggest that the motor representations of the individual digits are distributed widely throughout the M1 hand area. The specific fingers that were impaired were unrelated to the location of the inactivation along the central sulcus.
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A agonist muscimol were used to examine the effect of reversibly inactivating portions of the M1 hand area in monkeys. While the results are not directly related to recovery of function, they are highly relevant to our understanding of the behavioral effects of cortical injury in M1. The reversible lesions were focal, affecting only a portion of the M1 hand area. Such limited lesions are in contrast to the large lesions employed in most historical accounts of the effects of injury to M1, and provide key information regarding the distributed organization of motor representations. The results suggest that the motor representations of the individual digits are distributed widely throughout the M1 hand area. The specific fingers that were impaired were unrelated to the location of the inactivation along the central sulcus.
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Schieber, M.H.1
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The impairments in reaching and the movements of compensation in rats with motor cortex lesions: An endpoint, videorecording, and movement notation analysis
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Whishaw I.Q., Pellis S.M., Gorny B.P., Pellis V.C. The impairments in reaching and the movements of compensation in rats with motor cortex lesions: an endpoint, videorecording, and movement notation analysis. Behav Brain Res. 42:1991;77-91.
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Paw and limb use in skilled and spontaneous reaching after pyramidal tract, red nucleus and combined lesions in the rat: Behavioral and anatomical dissociations
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As in an earlier report [19], this study demonstrates the importance of kinematic analysis of movement patterns after injury to motor systems. Rats with pyramidal tract (PT) lesions had reduced success in food retrieval compared to rats with red nucleus (RN) lesions. Both PT and RN lesions resulted in impaired limb aiming, pronation and supination. However, RN lesions abolished a particular strategy of orienting the paw during searching and grasping for food (known as arpeggio movements). This study provides information on the differential contributions of the motor cortex and red nucleus to motor control. In addition, because it was found that rats with combined lesions could still perform food retrievals, this study provides additional support for the notion that a number of motor structures participate in the control of forelimb movement and could potentially be involved in motor recovery after injury.
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Whishaw I.Q., Gorny B., Sarna J. Paw and limb use in skilled and spontaneous reaching after pyramidal tract, red nucleus and combined lesions in the rat: behavioral and anatomical dissociations. Behav Brain Res. 93:1998;167-183. As in an earlier report [19], this study demonstrates the importance of kinematic analysis of movement patterns after injury to motor systems. Rats with pyramidal tract (PT) lesions had reduced success in food retrieval compared to rats with red nucleus (RN) lesions. Both PT and RN lesions resulted in impaired limb aiming, pronation and supination. However, RN lesions abolished a particular strategy of orienting the paw during searching and grasping for food (known as arpeggio movements). This study provides information on the differential contributions of the motor cortex and red nucleus to motor control. In addition, because it was found that rats with combined lesions could still perform food retrievals, this study provides additional support for the notion that a number of motor structures participate in the control of forelimb movement and could potentially be involved in motor recovery after injury.
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Behav Brain Res
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Whishaw, I.Q.1
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L. Goldstein. Armonk, New York: Futura. An outstanding comprehensive review of proposed theories to explain recovery of function after brain damage. The review defines and provides examples of diaschisis, compensation, unmasking, restitution and substitution of function, and synaptogensesis. Models of recovery are placed in historical context, beginning with von Monakow's theories of the 19th century.
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Stein D.G. Brain injury and theories of recovery. Goldstein L. Restorative Neurology: Advances in Pharmacotherapy for Recovery After Stroke. 1998;1-34 Futura, Armonk, New York. An outstanding comprehensive review of proposed theories to explain recovery of function after brain damage. The review defines and provides examples of diaschisis, compensation, unmasking, restitution and substitution of function, and synaptogensesis. Models of recovery are placed in historical context, beginning with von Monakow's theories of the 19th century.
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Whishaw I.Q., Coles B.L.K., Pellis S.M., Miklyaeva E.I. Impairments and compensation in mouth and limb use in free feeding after unilateral dopamine depletions in a rat analog of human Parkinson's disease. Behav Brain Res. 84:1997;167-177.
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•,27]. They found that motorperformance improved after CI therapy. In this study, they report that the injured hemisphere displays increased excitability and an enlarged representation of the abductor pollicis brevis muscle. These results parallel those obtained using electrophysiological techniques in non-human primates [29]. Namely, they suggest that the uninjured tissue adjacent to injury in the motor cortex undergoes functional plasticity and that this plasticity is adaptive in the sense that it is correlated with improved motor performance.
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•,27]. They found that motorperformance improved after CI therapy. In this study, they report that the injured hemisphere displays increased excitability and an enlarged representation of the abductor pollicis brevis muscle. These results parallel those obtained using electrophysiological techniques in non-human primates [29]. Namely, they suggest that the uninjured tissue adjacent to injury in the motor cortex undergoes functional plasticity and that this plasticity is adaptive in the sense that it is correlated with improved motor performance.
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Use dependent exacerbation of brain damage occurs during an early post-lesion vulnerable period
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Previous studies demonstrated that after injury to the sensorimotor cortex in rats, extreme overuse of the affected limb (by immobilization of the unaffected limb in a cast) can result in an enlargement of the lesion and further motor impairment [30]. This study defines the vulnerable period for use-dependent exacerbation of the injury in lesioned rats. Forced overuse of the impaired limb during the first 7 days after injury resulted in expansion of the injury and poorer motor performance. Forced overuse during the next 7 days did not result in injury expansion, but nonetheless resulted in poorer motor performance. This study strongly suggests that there are specific vulnerable periods for the maladaptive effects of impaired limb use after injury. The timing of these maladaptive effects must be considered along with the timing of adaptive effects in any rational therapeutic design for treatment of motor deficits after injury.
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Humm J.L., Kozlowski D.A., James D.C., Gotts J.E., Schallert T. Use dependent exacerbation of brain damage occurs during an early post-lesion vulnerable period. Brain Res. 783:1998;286-292. Previous studies demonstrated that after injury to the sensorimotor cortex in rats, extreme overuse of the affected limb (by immobilization of the unaffected limb in a cast) can result in an enlargement of the lesion and further motor impairment [30]. This study defines the vulnerable period for use-dependent exacerbation of the injury in lesioned rats. Forced overuse of the impaired limb during the first 7 days after injury resulted in expansion of the injury and poorer motor performance. Forced overuse during the next 7 days did not result in injury expansion, but nonetheless resulted in poorer motor performance. This study strongly suggests that there are specific vulnerable periods for the maladaptive effects of impaired limb use after injury. The timing of these maladaptive effects must be considered along with the timing of adaptive effects in any rational therapeutic design for treatment of motor deficits after injury.
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••]. MK-801 prevented the exacerbation of injury compared with vehicle controls. This finding suggests that use-dependent exaggeration of injury is mediated by NMDA-receptor hypersensitivity.
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••]. MK-801 prevented the exacerbation of injury compared with vehicle controls. This finding suggests that use-dependent exaggeration of injury is mediated by NMDA-receptor hypersensitivity.
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Immunocytochemical techniques were used to examine the expression of proteins associated with neural sprouting and synaptogenesis at various times (3 to 60 days) after middle cerebral artery and common carotid artery occlusion in the rat. The study specifically examined the effects of d-amphetamine administration on behavioral recovery and structural plasticity. The data are consistent with increased neurite growth and synaptogenesis as a result of d-amphetamine treatment. More direct measures of neuronal growth and synaptogenesis are needed to strengthen this hypothesis.
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Stroemer R.P., Kent T.A., Hulsebosch C.E. Enhanced neocortical neural sprouting, synaptogenesis, and behavioral recovery with D-amphetamine therapy after neocortical infarction in rats. Stroke. 29:1998;2381-2395. Immunocytochemical techniques were used to examine the expression of proteins associated with neural sprouting and synaptogenesis at various times (3 to 60 days) after middle cerebral artery and common carotid artery occlusion in the rat. The study specifically examined the effects of d-amphetamine administration on behavioral recovery and structural plasticity. The data are consistent with increased neurite growth and synaptogenesis as a result of d-amphetamine treatment. More direct measures of neuronal growth and synaptogenesis are needed to strengthen this hypothesis.
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Kawamata T., Ren J., Chan T.C.K., Charette M., Finklestein S.P. Intracisternal osteogenic protein-1 enhances functional recovery following focal stroke. Neuroreport. 9:1998;1441-1445. Osteogenic protein-1 (OP-1) was administered to rats after cortical damage induced by middle cerebral artery occlusion. Administration of OP-1 had no effect on infarct volume, but resulted in significant improvement in forelimb and hindlimb placing compared with vehicle controls. Neurotrophic factors have become increasingly popular for restoration of function after neuronal injury in animal models. They are particularly attractive for neurological treatment because of their relative specificity of effects. At least in culture, OP-1 appears to promote dendritic growth selectively. The major obstacle of neurotrophic factors is that they do not readily cross the blood-brain barrier, limiting delivery techniques to infusion directly into the central nervous system (e.g. directly into the ventricular space).
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A receptor-dependant synaptic inhibition. The amount of further potentiation that could be induced in the trained motor cortex was less than in controls. The authors argue that if LTP was induced during skill learning, further potentiation could be occluded during LTP induction in the slice preparation. These results suggest that intracortical horizontal connections are strengthened via LTP-like mechanisms during motor skill learning. Whereas a number of previous studies had examined the LTP-like and long-term depression (LTD)-like mechanisms of intracortical pathways in rat motor cortex slice preparations in (see e.g. [49,50]), this is the first study to demonstrate. that the strength of these connections is altered after motor skill learning. It is possible that similar mechanisms underlie cortical plasticity after injury.
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The authors report that 28 days after unilateral, permanent middle cerebral artery occlusion in mice, excitatory and inhibitory amino acid receptor densities are altered. Together with a companion article [64•], this study suggests that cortical injury results in long-term alterations in excitatory and inhibitory receptors in the cerebral cortex (i.e. an increase in the number of NMDA receptors and a decrease in GABA receptors). These changes take place in regions remote from the focal lesion. While these changes are thought to be pathophysiologic, it is intriguing to speculate that the neurotransmitter changes may be part of an adaptive process involved in functional reorganization [57].
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Qü M., Mittmann T., Luhmann H.J., Schleicher A., Zilles K. Long-term changes of ionotropic glutamate and GABA receptors after unilateral permanent focal cerebral ischemia in the mouse brain. Neuroscience. 85:1998;29-43. The authors report that 28 days after unilateral, permanent middle cerebral artery occlusion in mice, excitatory and inhibitory amino acid receptor densities are altered. Together with a companion article [64•], this study suggests that cortical injury results in long-term alterations in excitatory and inhibitory receptors in the cerebral cortex (i.e. an increase in the number of NMDA receptors and a decrease in GABA receptors). These changes take place in regions remote from the focal lesion. While these changes are thought to be pathophysiologic, it is intriguing to speculate that the neurotransmitter changes may be part of an adaptive process involved in functional reorganization [57].
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By examining orthodromic synaptic stimulation in neocortical slices from mice 28 days after permanent middle cerebral artery occlusion, the authors demonstrate that layer II/III pyramidal cells near the infarct exhibit pronounced hyperexcitability. A reduction in GABAergic inhibition was also found. These results are in agreement with hyperexcitablity changes in the rat after photothrombosis (see e.g. [58,59]). In addition, the data suggest that hyperexcitability changes are partially attributable to enhancement of NMDA receptors.
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In spontaneously hypertensive rats, the middle cerebral artery (MCA) was permanently ligated distal to the striatal branches. Twenty-four hours after MCA ligation, rats in an early training group were transferred to an enriched environment equipped with various objects, such as inclined boards and wooden blocks. In addition, for one hour per day, these rats received motor training to traverse a rotating pole, hang on a rope, and maintain balance on an inclined plane. Rats in a late training group were transferred to the same enriched environment and motor training schedule seven days after MCA ligation. Post-mortem examination of cortical tissue six weeks after the MCA ligation revealed that the cortical infarct volume was larger in the early training group compared to the late training group or a control group that received no training. This study suggests that use-dependent exaggeration of cortical injury may occur simply by early motor training.
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Risedal A., Zeng J., Johansson B.B. Early training may exacerbate brain damage after focal brain ischemia in the rat. J Cereb Blood Flow Metab. 19:1999;997-1003. In spontaneously hypertensive rats, the middle cerebral artery (MCA) was permanently ligated distal to the striatal branches. Twenty-four hours after MCA ligation, rats in an early training group were transferred to an enriched environment equipped with various objects, such as inclined boards and wooden blocks. In addition, for one hour per day, these rats received motor training to traverse a rotating pole, hang on a rope, and maintain balance on an inclined plane. Rats in a late training group were transferred to the same enriched environment and motor training schedule seven days after MCA ligation. Post-mortem examination of cortical tissue six weeks after the MCA ligation revealed that the cortical infarct volume was larger in the early training group compared to the late training group or a control group that received no training. This study suggests that use-dependent exaggeration of cortical injury may occur simply by early motor training.
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