Influence of an Enriched Environment and Cortical Grafting on Functional Outcome in Brain Infarcts of Adult Rats

Grabowski, Martin; Sørensen, Jens Christian; Mattsson, Bengt; Zimmer, Jens; Johansson, Barbro

doi:10.1006/exnr.1995.1011

Cited by 95 publications

(51 citation statements)

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“…Stroke rats displayed mild spontaneous rotation to the right, possibly reflecting a stronger push by the unaffected left paw, 6 whereas dopamine agonist drugs induced marked rotation to the left, consistent with activation of dopamine receptors on the intact side of the brain. Neither asymmetry was evident in grafted rats.…”

Section: Veizovic Et Al Stem Cells Grafted Into Intact Hemisphere Redmentioning

confidence: 82%

“…Primary fetal grafts have been shown to improve motor performance after cortical infarction 6,7,21 or striatal lesions, 22 but this may only be significant when grafts have been paired with enriched environments or training, pointing to a role for experience-dependent neuronal plasticity in recovery. 3,4 Indeed, Grabowski et al 6 found that an enriched environment was as functionally effective as fetal neocortical grafts, with no additive effects apparent.…”

Section: Bilateral Asymmetrymentioning

confidence: 99%

“…3,4 Indeed, Grabowski et al 6 found that an enriched environment was as functionally effective as fetal neocortical grafts, with no additive effects apparent. The mechanisms are not well understood, although Mayer et al 22 suggest that training enables animals to learn how to use their transplants.…”

Section: Bilateral Asymmetrymentioning

confidence: 99%

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Resolution of Stroke Deficits Following Contralateral Grafts of Conditionally Immortal Neuroepithelial Stem Cells

Veizovic

Beech²,

Stroemer³

et al. 2001

Stroke

204

118

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Background and Purpose-Grafts of MHP36 cells have previously been shown to reduce dysfunction after global ischemia in rats. To test their efficacy after focal ischemia, MHP36 cells were grafted 2 to 3 weeks after transient intraluminal middle cerebral artery occlusion (tMCAO) in rats. Methods-MHP36 cells were implanted into the hemisphere contralateral to the lesion, with 8 deposits of 3 L of cell suspension (25 000 cells per microliter). Sham grafted rats received equivalent volumes of vehicle. Three groups, sham-operated controls (nϭ11), MCAOϩsham grafts (nϭ10), and MCAOϩMHP36 grafts (nϭ11), were compared in 3 behavioral tests. Results-In the bilateral asymmetry test, MCAOϩMHP36 grafted rats exhibited neglect before grafting but subsequently showed no significant dysfunction, whereas MCAOϩsham grafted rats showed stable sensorimotor deficits over 18 weeks relative to controls. MCAOϩsham grafted rats demonstrated spontaneous motor asymmetry and increased rotational bias after injection of dopamine agonists. MCAOϩMHP36 and control groups exhibited no bias in either spontaneous or drug-induced rotation. In contrast to motor recovery, MCAOϩMHP36 grafted rats showed no improvement relative to MCAOϩsham grafted rats in spatial learning and memory in the water maze. MCAO produced large striatal and cortical cavitations in both occluded groups. Lesion volume was significantly reduced (PϽ0.05) in the MCAOϩMHP36 grafted group. The majority of MHP36 cells were identified within the intact grafted hemisphere. However, MHP36 cells were also seen in the cortex, striatum, and corpus callosum of the lesioned hemisphere. Conclusions-MHP36 cells may improve functional outcome after MCAO by assisting spontaneous reorganization in both the damaged and intact hemispheres.

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Section: Veizovic Et Al Stem Cells Grafted Into Intact Hemisphere Redmentioning

confidence: 82%

Section: Bilateral Asymmetrymentioning

confidence: 99%

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Resolution of Stroke Deficits Following Contralateral Grafts of Conditionally Immortal Neuroepithelial Stem Cells

Veizovic

Beech²,

Stroemer³

et al. 2001

Stroke

204

118

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“…Six-month-old male SHR, obtained from Mollegard Breeding Center, Ejby, Denmark, 2 months earlier and preoperatively housed in standard cages (550 × 350 × 200 mm, 3 to 4 rats in each cage), were anesthetized with methohexital sodium (Brietal, 37°C) 50 mg/kg intraperitoneally. The right MCA was accessed via a small craniotomy, and the artery was ligated distal to the striatal branches (Coyle, 1982;Grabowski et al, 1995), causing a neocortical infarct (Fig. 1, top right).…”

Section: Animals Housing Conditions and Surgerymentioning

confidence: 99%

Effects of Cortical Ischemia and Postischemic Environmental Enrichment on Hippocampal Cell Genesis and Differentiation in the Adult Rat

Komitova

Perfilieva

Mattsson

et al. 2002

J Cereb Blood Flow Metab

Self Cite

103

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Summary:The study aimed to elucidate the effects of cortical ischemia and postischemic environmental enrichment on hippocampal cell genesis. A cortical infarct was induced by a permanent ligation of the middle cerebral artery distal to the striatal branches in 6-month-old spontaneously hypertensive rats. Bromodeoxyuridine (BrdU) was administered as 7 consecutive daily injections starting 24 hours after surgery and animals were housed in standard or enriched environment. Four weeks after completed BrdU administration, BrdU incorporation and its co-localization with the neuronal markers NeuN and calbindin D28k, and the astrocytic marker glial fibrillary acidic protein in the granular cell layer and subgranular zone of the hippocampal dentate gyrus were determined with immunohistochemistry and were quantified stereologically. Compared with sham-operated rats, rats with cortical infarcts had a fiveto sixfold ipsilateral increase in BrdU-labeled cells. About 80% of the new cells were neurons. Differential postischemic housing did not influence significantly the total number of surviving BrdU-labeled cells or newborn neurons. However, postischemic environmental enrichment increased the ipsilateral generation of astrocytes normalizing the astrocyte-to-neuron ratio, which was significantly reduced in rats housed in standard environment postischemically.

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“…Housing several rats in an enriched environment after an experimental stroke, allowing both social interaction and physical activity, improves functional outcome compared with rats housed in standard cages (Johansson, 1996;Ohlsson and Johansson, 1995). This effect of enriched environment is not because of a decrease in infarct volume because the size of the brain infarct is the same in animals housed in standard cages and in those in enriched environment (Grabowski et al, 1995;Ohlsson and Johansson, 1995). Rather, the enriched environment causes structural changes of neurons such as increased spine density, dendritic branching, and cell genesis (Biernaskie and Corbett, 2001;Johansson and Belichenko, 2002;Komitova et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Enriched Environment Enhances Recovery of Motor Function after Focal Ischemia in Mice, and Downregulates the Transcription Factor NGFI-A

Nygren

Wieloch

2005

J Cereb Blood Flow Metab

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The purpose of this study was to investigate the effect of enriched environment on motor function after experimental stroke in mice, and to determine whether time in enriched environment affects functional recovery. Earlier investigations have shown that rats placed in an enriched environment after focal ischemia, remarkably improve motor function, but similar observations in mice have not been reported. In this study, we show that placing mice in an enriched environment for 3 h daily for 2 weeks, after transient (50 mins) occlusion of the middle cerebral artery, enhanced neurologic outcome. Continuous postischemic housing in the enriched environment likewise improved motor function, but mortality increased. Two weeks exposure to enriched environment followed by housing the mice in standard cages for 2 weeks, resulted in a loss of the improved motor function. In contrast, 4 weeks exposure to enriched environment led to an improved motor function and to a better maintenance of neurologic recovery. The expression levels of the immediate-early gene nerve growth factor-induced gene A at 2 to 3 weeks of recovery decreased in animals housed in enriched environment, implying this transcription factor in the recovery process. We conclude that housing mice in an enriched environment after experimental stroke improves functional outcome. Also, the presented experimental procedure is useful for further studies of the genomics of functional recovery after experimental stroke.

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Influence of an Enriched Environment and Cortical Grafting on Functional Outcome in Brain Infarcts of Adult Rats

Cited by 95 publications

References 0 publications

Resolution of Stroke Deficits Following Contralateral Grafts of Conditionally Immortal Neuroepithelial Stem Cells

Resolution of Stroke Deficits Following Contralateral Grafts of Conditionally Immortal Neuroepithelial Stem Cells

Effects of Cortical Ischemia and Postischemic Environmental Enrichment on Hippocampal Cell Genesis and Differentiation in the Adult Rat

Enriched Environment Enhances Recovery of Motor Function after Focal Ischemia in Mice, and Downregulates the Transcription Factor NGFI-A

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