Mechanisms Underlying Functional Recovery Following Stroke

Lee, R G; Donkelaar, Paul

doi:10.1017/s0317167100039445

Cited by 142 publications

(73 citation statements)

References 39 publications

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“…This possibility is supported by various changes known to occur in distant areas after a central lesion (Chollet et al, 1991;Lee and van Donkelaar, 1995;Witte and Stoll, 1997;Nudo, 1999). Particularly, the premotor cortex has been suggested to play an active role in motor recovery after stroke in nonhuman primates (Liu and Rouiller, 1999;Frost et al, 2003) and humans (Miyai et al, 1999(Miyai et al, , 2002.…”

Section: Introductionmentioning

confidence: 95%

Extensive Cortical Rewiring after Brain Injury

Dancause¹,

Barbay²,

Frost³

et al. 2005

J. Neurosci.

629

476

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Previously, we showed that the ventral premotor cortex (PMv) underwent neurophysiological remodeling after injury to the primary motor cortex (M1). In the present study, we examined cortical connections of PMv after such lesions. The neuroanatomical tract tracer biotinylated dextran amine was injected into the PMv hand area at least 5 months after ischemic injury to the M1 hand area. Comparison of labeling patterns between experimental and control animals demonstrated extensive proliferation of novel PMv terminal fields and the appearance of retrogradely labeled cell bodies within area 1/2 of the primary somatosensory cortex after M1 injury. Furthermore, evidence was found for alterations in the trajectory of PMv intracortical axons near the site of the lesion. The results suggest that M1 injury results in axonal sprouting near the ischemic injury and the establishment of novel connections within a distant target. These results support the hypothesis that, after a cortical injury, such as occurs after stroke, cortical areas distant from the injury undergo major neuroanatomical reorganization. Our results reveal an extraordinary anatomical rewiring capacity in the adult CNS after injury that may potentially play a role in recovery.

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Section: Introductionmentioning

confidence: 95%

Extensive Cortical Rewiring after Brain Injury

Dancause¹,

Barbay²,

Frost³

et al. 2005

J. Neurosci.

629

476

View full text Add to dashboard Cite

show abstract

“…The amount of dendritic growth in the undamaged motor cortex was associated with both lesion size and improved functional outcome. Neuronal reorganization within this region likely reflects unmasking and reorganization of ipsilateral corticospinal projections (Lee and van Donkelaar, 1995) or axonal sprouting and formation of novel subcortical projections (Kawamata et al, 1997;Chen et al, 2002;Papadopoulos et al, 2002). Although it is conceivable that recovery could be supported by the minimal ipsilateral (uncrossed) projections from the undamaged motor cortex to cervical spinal cord, it is more likely that the corticofugal sprouting from the undamaged motor cortex to the red nucleus (on the affected side) is contributing to improved function Papadopoulos et al, 2002).…”

Section: Early Rehabilitation (Er5) Does Not Exacerbate Infarct Size mentioning

confidence: 99%

Efficacy of Rehabilitative Experience Declines with Time after Focal Ischemic Brain Injury

Biernaskie¹,

Chernenko²,

Corbett³

2004

J. Neurosci.

604

463

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To maximize the effectiveness of rehabilitative therapies after stroke, it is critical to determine when the brain is most responsive (i.e., plastic) to sensorimotor experience after injury and to focus such efforts within this period. Here, we compared the efficacy of 5 weeks of enriched rehabilitation (ER) initiated at 5 d (ER5), ER14, or ER30 after focal ischemia, as judged by functional outcome and neuromorphological change. ER5 provided marked improvement in skilled forelimb reaching ability and ladder-rung-and narrow-beam-walking tasks and attenuated the stroke-induced reliance on the unaffected forepaw for postural support. ER14 provided improvement to a somewhat lesser extent, whereas recovery was diminished after ER30 such that motor function did not differ from ischemic animals exposed to social housing.To examine potential neural substrates of the improved function, we examined dendritic morphology in the undamaged motor cortex because our previous work (Biernaskie and Corbett, 2001) suggested that recovery was associated with enhanced dendritic growth in this region. ER5 increased the number of branches and complexity of layer V neurons compared with both social housing and control animals. Dendritic arbor after ER14 (although increased) and ER30 did not differ from those exposed to social housing. These data suggest that the poststroke brain displays heightened sensitivity to rehabilitative experience early after the stroke but declines with time. These findings have important implications for rehabilitation of stroke patients, many of whom experience considerable delays before therapy is initiated.

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“…After an ischemic attack, a majority of stroke patients exhibit certain levels of motor weakness and sensory disturbances; however, over time, most will show a certain degree of functional recovery [28,63]. The results of several animal and human studies on stroke have revealed that post stroke recovery and restoration of function may be explained by brain reorganization and brain plasticity [63,82,126,129]. As suggested by Lledo and colleagues [86], brain plasticity refers to the brain ability to change its structure and function during maturation, learning, environmental changes and pathology.…”

Section: Brain Plasticity and Post Stroke Recoverymentioning

confidence: 99%

Inflammation, plasticity and real-time imaging after cerebral ischemia

2009

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With an incidence of approximately 350 in 100,000, stroke is the third leading cause of death and a major cause of disability in industrialized countries. At present, although progress has been made in understanding the molecular pathways that lead to ischemic cell death, the current clinical treatments remain poorly eVective. There is mounting evidence that inXammation plays an important role in cerebral ischemia. Experimentally and clinically, brain response to ischemic injury is associated with an acute and prolonged inXammatory process characterized by the activation of resident glial cells, production of inXammatory cytokines as well as leukocyte and monocyte inWltration in the brain, events that may contribute to ischemic brain injury and aVect brain recovery and plasticity. However, whether the post-ischemic inXammatory response is deleterious or beneWcial to brain recovery is presently a matter of debate and controversies. Here, we summarize the current knowledge on the molecular mechanisms underlying post-ischemic neuronal plasticity and the potential role of inXammation in regenerative processes and functional recovery after stroke. Furthermore, because of the dynamic nature of the brain inXammatory response, we highlight the importance of the development of novel experimental approaches such as real-time imaging. Finally, we discuss the novel transgenic reporter mice models that have allowed us to visualize and to analyze the processes such as neuroinXammation and neuronal repair from the ischemic brains of live animals.

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Mechanisms Underlying Functional Recovery Following Stroke

Cited by 142 publications

References 39 publications

Extensive Cortical Rewiring after Brain Injury

Extensive Cortical Rewiring after Brain Injury

Efficacy of Rehabilitative Experience Declines with Time after Focal Ischemic Brain Injury

Inflammation, plasticity and real-time imaging after cerebral ischemia

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