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  • 1
    In: Frontiers in Cellular Neuroscience, Frontiers Media SA, Vol. 7 ( 2014)
    Type of Medium: Online Resource
    ISSN: 1662-5102
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2014
    detail.hit.zdb_id: 2452963-1
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  • 2
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 47, No. 3 ( 2016-03), p. 852-862
    Abstract: Bone marrow cell (BMC)–based therapies, either the transplantation of exogenous cells or stimulation of endogenous cells by growth factors like the granulocyte colony–stimulating factor (G-CSF), are considered a promising means of treating stroke. In contrast to large preclinical evidence, however, a recent clinical stroke trial on G-CSF was neutral. We, therefore, aimed to investigate possible synergistic effects of co-administration of G-CSF and BMCs after experimental stroke in mice to enhance the efficacy compared with single treatments. Methods— We used an animal model for experimental stroke as paradigm to study possible synergistic effects of co-administration of G-CSF and BMCs on the functional outcome and the pathophysiological mechanism. Results— G-CSF treatment alone led to an improved functional outcome, a reduced infarct volume, increased blood vessel stabilization, and decreased overall inflammation. Surprisingly, the combination of G-CSF and BMCs abrogated G-CSFs’ beneficial effects and resulted in increased hemorrhagic infarct transformation, altered blood–brain barrier, excessive astrogliosis, and altered immune cell polarization. These increased rates of infarct bleeding were mainly mediated by elevated matrix metalloproteinase-9–mediated blood–brain barrier breakdown in G-CSF- and BMCs-treated animals combined with an increased number of dilated and thus likely more fragile vessels in the subacute phase after cerebral ischemia. Conclusions— Our results provide new insights into both BMC-based therapies and immune cell biology and help to understand potential adverse and unexpected side effects.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2016
    detail.hit.zdb_id: 1467823-8
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  • 3
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 45, No. 1 ( 2014-01), p. 239-247
    Abstract: Although several studies have shown beneficial effects of training in animal stroke models, the most effective training strategy and the optimal time to initiate training have not been identified. The present meta-analysis was performed to compare the efficacy of different training strategies and to determine the optimal time window for training in animal stroke models. Methods— We searched the literature for studies analyzing the efficacy of training in animal models of ischemic stroke. Training was categorized into forced physical training, voluntary physical training, constraint-induced movement therapy, and skilled reaching training. Two reviewers independently extracted data on study quality, infarct size, and neurological outcome. Data were pooled by means of a meta-analysis. Results— Thirty-five studies with 〉 880 animals were included. A meta-analysis of all treatments showed that training reduced the infarct volume by 14% (95% confidence interval, 2%–25%) and improved the cognitive function by 33% (95% confidence interval, 8%–50%), the neuroscore by 13.4% (95% confidence interval, 1.5%–25.3%), and the running function by 6.6% (95% confidence interval, 1.4%–11.9%). Forced physical training reduced the infarct volume and enhanced the running function most effectively, whereas skilled reaching training improved the limb function most effectively. A meta-regression illustrated that training was particularly efficacious when initiated between 1 and 5 days after stroke onset. Conclusions— Our meta-analysis confirms that training reduces the infarct volume and improves the functional recovery in animal stroke models. Forced physical training and skilled reaching training were identified as particularly effective training strategies. The efficacy of training is time dependent.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2014
    detail.hit.zdb_id: 1467823-8
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  • 4
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 42, No. 6 ( 2011-06), p. 1757-1763
    Abstract: Intravenous neural progenitor cell (NPC) treatment was shown to improve functional recovery after experimental stroke. The underlying mechanisms, however, are not completely understood so far. Here, we investigated the effects of systemic NPC transplantation on endogenous neurogenesis and dendritic plasticity of host neurons. Methods— Twenty-four hours after photothrombotic ischemia, adult rats received either 5 million NPC or placebo intravenously. Behavioral tests were performed weekly up to 4 weeks after ischemia. Endogenous neurogenesis, dendritic length, and dendritic branching of cortical pyramid cells and microglial activation were quantified. Results— NPC treatment led to a significantly improved sensorimotor function measured by the adhesive removal test. The dendritic length and the amount of branch points were significantly increased after NPC transplantation, whereas endogenous neurogenesis was decreased compared to placebo therapy. Decreased endogenous neurogenesis was associated with an increased number of activated microglial cells. Conclusions— Our findings suggest that an increased dendritic plasticity might be the structural basis of NPC-induced functional recovery. The decreased endogenous neurogenesis after NPC treatment seems to be mediated by microglial activation.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2011
    detail.hit.zdb_id: 1467823-8
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  • 5
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 45, No. 2 ( 2014-02), p. 614-618
    Abstract: Despite a high incidence of poststroke dementia, there is no specific treatment for this condition. Because the evaluation of poststroke cognitive deficits in animal models of stroke is exceedingly challenging, the preclinical evaluation of candidate drugs is limited. We aimed to explore the impact of small cortical photothrombotic strokes on poststroke cognition, thereby assessing the suitability of this experimental stroke model for the investigation of cognitive impairment after stroke. Methods— Photothrombotic cortical infarcts were induced in 19 adult male Wistar rats. Nineteen sham-operated animals served as controls. Using the Morris water maze, we analyzed the impact of photothrombotic stroke on both the acquisition of new memories and the recall of previously acquired memories. The cylinder test, the adhesive tape removal test, and the rotarod test were performed to investigate sensorimotor deficits. Results— Photothrombotic stroke significantly impaired the recall of previously acquired memories ( P 〈 0.05), whereas the acquisition of new memories remained largely intact. The analysis of the animals’ swimming speed in the water maze and the rotarod test showed no confounding motor impairments after photothrombotic stroke. The adhesive tape removal test and the cylinder test revealed mild sensorimotor deficits in lesioned animals ( P 〈 0.05). Conclusions— Photothrombotic cortical infarcts impair the recall of memories acquired before stroke, whereas the formation of new memories remains unimpaired. The observed deficits in the water maze are not confounded by disturbed motor functions. Overall, experimental photothrombotic strokes are well suited for the investigation of specific cognitive impairments after stroke.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2014
    detail.hit.zdb_id: 1467823-8
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  • 6
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 43, No. 4 ( 2012-04), p. 1137-1139
    Abstract: Sleep-related breathing disorders occur frequently after stroke. We assessed the feasibility of continuous positive airway pressure (CPAP) treatment initiated in the first night after stroke. Methods— In this open-label, parallel-group trial, 50 patients were randomly assigned to the CPAP therapy or to the control group. All patients underwent polysomnography in the fourth night. Intervention patients received CPAP therapy for 3 nights starting the first night after stroke onset and for an additional 4 nights when polysomnography revealed an apnea–hypopnea index 〉 10/hour. The primary end point was feasibility defined as apnea–hypopnea index reduction under CPAP treatment, nursing workload, and CPAP adherence. Results— The apnea–hypopnea index under CPAP treatment was significantly reduced (32.2±25.3–9.8±6.6, P =0.0001). Nursing workload did not significantly differ between the CPAP (n=25) and the control group (n=25; P =0.741). Ten patients (40.0%) had excellent CPAP use, 14 patients (56.0%) had some use, and 1 patient (4.0%) had no use. There was a trend toward greater National Institutes of Health Stroke Scale score improvement until Day 8 in patients on CPAP (2.00 versus 1.40, P =0.092) and a significantly greater National Institutes of Health Stroke Scale score improvement in patients with excellent CPAP use when compared with control patients (2.30 versus 1.40, P =0.022). Conclusions— CPAP therapy initiated in the first night after stroke seems to be feasible and was not associated with neurological deterioration. Clinical Trial Registration— URL: www.clinicaltrials.gov . Unique identifier: NCT00151177.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2012
    detail.hit.zdb_id: 1467823-8
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  • 7
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2012
    In:  Experimental & Translational Stroke Medicine Vol. 4, No. 1 ( 2012-12)
    In: Experimental & Translational Stroke Medicine, Springer Science and Business Media LLC, Vol. 4, No. 1 ( 2012-12)
    Type of Medium: Online Resource
    ISSN: 2040-7378
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2012
    detail.hit.zdb_id: 2520967-X
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