Use-dependent exacerbation of brain damage occurs during an early post-lesion vulnerable period

Humm, J. Leigh; Kozlowski, Dorothy A.; James, Debra C.; Gotts, Jeffrey E.; Schallert, Timothy

doi:10.1016/s0006-8993(97)01356-5

Cited by 233 publications

(129 citation statements)

References 25 publications

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“…The latter result raises the possibility of a limit on the amount of RA training that is beneficial. Expansion of neural injury and reduced restoration of function associated with early forced use of a forelimb after unilateral brain injury has been seen in rats [37][38][39][40]. Although the applicability of these results to human trials has not been demonstrated, they point out the need to consider intensity, total dose, and timing of training in trials of novel therapeutic methods and devices.…”

Section: Discussionmentioning

confidence: 97%

Robot-assisted upper-limb therapy in acute rehabilitation setting following stroke: Department of Veterans Affairs multisite clinical trial

Burgar¹,

Lum²,

Scremin³

et al. 2011

JRRD

152

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Abstract-This randomized, controlled, multisite Department of Veterans Affairs clinical trial assessed robot-assisted (RA) upper-limb therapy with the Mirror Image Movement Enabler (MIME) in the acute stroke rehabilitation setting. Hemiparetic subjects (n = 54) received RA therapy using MIME for either up to 15 hours (low-dose) or 30 hours (high-dose) or received up to 15 hours of additional conventional therapy in addition to usual care (control). The primary outcome measure was the FuglMeyer Assessment (FMA). The secondary outcome measures were the Functional Independence Measure (FIM), Wolf Motor Function Test, Motor Power, and Ashworth scores at intake, discharge, and 6-month follow-up. Mean duration of study treatment was 8.6, 15.8, and 9.4 hours for the low-dose, high-dose, and control groups, respectively. Gains in the primary outcome measure were not significantly different between groups at follow-up. Significant correlations were found at discharge between FMA gains and the dose and intensity of RA. Intensity also correlated with FMA gain at 6 months. The high-dose group had greater FIM gains than controls at discharge and greater tone but no difference in FIM changes compared with low-dose subjects at 6 months. As used during acute rehabilitation, motor-control changes at follow-up were no less with MIME than with additional conventional therapy. Intensity of training with MIME was positively correlated with motor-control gains.Clinical Trial Registration: ClinicalTrials.gov, NCT00223808, "Assisted Movement Neuro-rehabilitation: VA Multi-site Clinical Trial"; http://www.clinicaltrials.gov/ct2/show/NCT00223808

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Section: Discussionmentioning

confidence: 97%

Robot-assisted upper-limb therapy in acute rehabilitation setting following stroke: Department of Veterans Affairs multisite clinical trial

Burgar¹,

Lum²,

Scremin³

et al. 2011

JRRD

152

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“…The 14 day delay in the onset of the CS and training after the infarcts was chosen for its translational relevance and also to avoid a time window in which peri-infarct tissue has been found to be sensitive to overuse of the forelimb (Humm et al, 1998). The intensity and duration of the reach training after lesion combined with CS were chosen because this combination was previously found to improve reaching function after SMC lesions .…”

Section: Reach Training Methodsmentioning

confidence: 99%

Motor cortical stimulation promotes synaptic plasticity and behavioral improvements following sensorimotor cortex lesions

Adkins

Hsu

Jones

2008

Experimental Neurology

121

133

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Cortical stimulation (CS) as a means to modulate regional activity and excitability in cortex is emerging as a promising approach for facilitating rehabilitative interventions after brain damage, including stroke. In this study, we investigated whether CS-induced functional improvements are linked with synaptic plasticity in peri-infarct cortex and vary with the severity of impairments. Adult rats that were proficient in skilled reaching received subtotal unilateral ischemic sensorimotor cortex (SMC) lesions and implantation of chronic epidural electrodes over remaining motor cortex. Based on the initial magnitude of reaching deficits, rats were divided into severely and moderately impaired subgroups. Beginning two weeks post-surgery, rats received 100 Hz cathodal CS at 50% of movement thresholds or no-stimulation control procedures (NoCS) during 18 days of rehabilitative training on a reaching task. Stereological electron microscopy methods were used to quantify axodendritic synapse subtypes in motor cortical layer V underlying the electrode. In moderately, but not severely impaired rats, CS significantly enhanced recovery of reaching success. Sensitive movement analyses revealed that CS partially normalized reaching movements in both impairment subgroups compared to NoCS. Additionally, both CS subgroups had significantly greater density of axodendritic synapses and moderately impaired CS rats had increases in presumed efficacious synapse subtypes (perforated and multiple synapses) in stimulated cortex compared to NoCS. Synaptic density was positively correlated with postrehabilitation reaching success. In addition to providing further support that CS can promote functional recovery, these findings suggest that CS-induced functional improvements may be mediated by synaptic structural plasticity in stimulated cortex.Keywords motor rehabilitation; skilled reaching; synaptic plasticity; perforated synapses; multisynaptic boutons; stroke Motor impairments are among the most common disabilities caused by stroke (Thom et al., 2006). Motor rehabilitative training can reduce these impairments but it is often insufficient * Corresponding author. The University of Texas, 1 University Station A8000, Austin, TX 78712. Phone: +1 512 475-7763, Fax: +1 512 475-7765, dladkins@mail.utexas.edu. ‡ D.L.A and J.E.H. contributed equally to this work.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptExp Neurol. Author manuscript; available in PMC 2011 January 10. to restore normal levels of function (Duncan et al., 2000;Dobkin, 2004). Recent studies in ...

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“…It also promotes the remodeling of synapses in the hippocampus (Liu et al, 2011). Astrocytes play an important role in this process (Humm et al, 1998;Taskapiliogly et al, 2009) by synthesizing glial-derived neurotrophic factor, which is responsible for the increased survival of dopaminergic neurons and by promoting neuroplasticity (Senna et al, 2011;Henderson et al, 1994;Lin et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

Effect of Exercise Prior or After Ischemia on the Density of Neurons and Astrocytes in the Brain of Rats

Damázio¹,

Melo²,

Lima³

et al. 2014

American Journal of Neuroscience

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The aim of this study was to analyse the density of astrocytes and neurons in the motor areas of the cortex, striatum and hippocampus of rats that performed exercise before or after cerebral ischemia. A total of 36 Wistar rats were separated into two groups: One that was subjected to Middle Cerebral Artery Occlusion (MCAO) and the other that underwent surgical access in the absence of ischemia. Both groups were subdivided into: Animals that underwent exercise prior to MCAO and sham surgery (AI and AC, n = 12); animals that underwent exercise after MCAO and sham surgery (DI and DC, n = 12); and animals that did not undergo exercise (SI and SC, n = 12). The brains of mice were sectioned and stained by the Nissl method for staining of neurons and the astrocytes were labeled by immunohistochemistry with glial fibrillary acidic protein. Physical training was conducted after the surgery for 6 weeks (30 min/day), 5 days per week. The animals exercised before cerebral ischemia showed greater density of neurons in the striatum, in the apex of the dentate gyrus of the hippocampus, in the motor cortex contra lateral to the lesion and more astrocytes in the motor cortex of the cerebral hemispheres compared with the untrained group (p<0.05). The density of neurons in the brain regions analysed remained unchanged in exercised animals from the fourth day after cerebral ischemia when compared with the sedentary group.

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Use-dependent exacerbation of brain damage occurs during an early post-lesion vulnerable period

Cited by 233 publications

References 25 publications

Robot-assisted upper-limb therapy in acute rehabilitation setting following stroke: Department of Veterans Affairs multisite clinical trial

Robot-assisted upper-limb therapy in acute rehabilitation setting following stroke: Department of Veterans Affairs multisite clinical trial

Motor cortical stimulation promotes synaptic plasticity and behavioral improvements following sensorimotor cortex lesions

Effect of Exercise Prior or After Ischemia on the Density of Neurons and Astrocytes in the Brain of Rats

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