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  • Schmidt, Antje  (12)
  • Strecker, Jan-Kolja  (12)
  • 1
    In: Frontiers in Behavioral Neuroscience, Frontiers Media SA, Vol. 11 ( 2017-03-16)
    Materialart: Online-Ressource
    ISSN: 1662-5153
    Sprache: Unbekannt
    Verlag: Frontiers Media SA
    Publikationsdatum: 2017
    ZDB Id: 2452960-6
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 2
    Online-Ressource
    Online-Ressource
    Ovid Technologies (Wolters Kluwer Health) ; 2015
    In:  Stroke Vol. 46, No. 4 ( 2015-04), p. 1127-1131
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 46, No. 4 ( 2015-04), p. 1127-1131
    Kurzfassung: In spite of its high disease burden, there is no specific treatment for multi-infarct dementia. The preclinical evaluation of candidate drugs is limited because an appropriate animal model is lacking. Therefore, we aimed to evaluate whether a mouse model of recurrent photothrombotic stroke is suitable for the preclinical investigation of multi-infarct dementia. Methods— Recurrent photothrombotic cortical infarcts were induced in 25 adult C57BL/6 mice. Twenty-five sham-operated animals served as controls. The object recognition test and the Morris water maze test were performed 〉 6 weeks to assess cognitive deficits. Afterward, histological analyses were performed to characterize histopathologic changes associated with recurrent photothrombotic infarcts. Results— After the first infarct, the object recognition test showed a trend toward an impaired formation of recognition memories ( P =0.08), and the Morris Water Maze test revealed significantly impaired spatial learning and memory functions ( P 〈 0.05). After recurrent infarcts, the object recognition test showed significant recognition memory deficits ( P 〈 0.001) and the Morris water maze test demonstrated persisting spatial learning and memory deficits ( P 〈 0.05). Histological analyses revealed remote astrogliosis in the hippocampus. Conclusions— Our results show progressive cognitive deficits in a mouse model of recurrent photothrombotic stroke. The presented model resembles the clinical features of human multi-infarct dementia and enables the investigation of its pathophysiological mechanisms and the evaluation of treatment strategies.
    Materialart: Online-Ressource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Sprache: Englisch
    Verlag: Ovid Technologies (Wolters Kluwer Health)
    Publikationsdatum: 2015
    ZDB Id: 1467823-8
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 3
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 47, No. 3 ( 2016-03), p. 852-862
    Kurzfassung: 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.
    Materialart: Online-Ressource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Sprache: Englisch
    Verlag: Ovid Technologies (Wolters Kluwer Health)
    Publikationsdatum: 2016
    ZDB Id: 1467823-8
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 4
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 45, No. 1 ( 2014-01), p. 239-247
    Kurzfassung: 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.
    Materialart: Online-Ressource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Sprache: Englisch
    Verlag: Ovid Technologies (Wolters Kluwer Health)
    Publikationsdatum: 2014
    ZDB Id: 1467823-8
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 5
    In: Frontiers in Cellular Neuroscience, Frontiers Media SA, Vol. 7 ( 2014)
    Materialart: Online-Ressource
    ISSN: 1662-5102
    Sprache: Unbekannt
    Verlag: Frontiers Media SA
    Publikationsdatum: 2014
    ZDB Id: 2452963-1
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 6
    Online-Ressource
    Online-Ressource
    Ovid Technologies (Wolters Kluwer Health) ; 2014
    In:  Stroke Vol. 45, No. suppl_1 ( 2014-02)
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 45, No. suppl_1 ( 2014-02)
    Kurzfassung: Introduction: The peptide hormone Ghrelin is known as the ligand of the growth hormone secretagogue receptor and affects pituitary hormone secretion, gastrointestinal function and the cardiovascular and immune system. Recently it has been shown that Ghrelin also influences key mechanisms of the CNS. Ghrelin crosses the blood-brain barrier and binds to hippocampal neurons thereby promoting dendritic spine synapse formation and proliferation of progenitor cells. These finings led to the assumption that Ghrelin might exert neuroprotective and neuroregenerative effects in the brain. We assessed the hypothesis that a chronic pharmacological stimulation with Ghrelin promotes mechanisms of long term post-stroke neuroregeneration thereby improving functional and structural regeneration. Methods: In order to examine long term neuroregenerative effects, Ghrelin (40 μg/kg/d) was administered starting 24 hours after photothrombotic ischemia until the end of the experiment via osmotic pumps. Functional recovery was assessed by the adhesive tape removal test and the cylinder test performed weekly for 4 weeks. Cognitive function was analysed using the Morris water maze test. Brains were removed 4 weeks after ischemia. Post-ischemic neurogenesis was quantified in the subventricular zone (SVZ) and dentate gyrus (DG) using antibodies against Bromodeoxyuridine and Doublecortin. Results: Treatment with Ghrelin improved motoric and cognitive recovery following photothrombotic stroke. In close apposition to the enhanced functional recovery, the pharmacological stimulation with Ghrelin significantly increased the generation of newborn hippocampal neurons in the SVZ as well as in the DG of the hippocampus. Conclusion: In the present study, we demonstrated that chronic treatment with Ghrelin promotes the structural and functional recovery following ischemia. The recently discovered neurotrophic properties and the effects on post-stroke recovery demonstrated in this study substantiate the potential of Ghrelin as a promising agent for the neuroregenerative treatment of ischemic stroke.
    Materialart: Online-Ressource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Sprache: Englisch
    Verlag: Ovid Technologies (Wolters Kluwer Health)
    Publikationsdatum: 2014
    ZDB Id: 1467823-8
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 7
    Online-Ressource
    Online-Ressource
    Elsevier BV ; 2017
    In:  Neurochemistry International Vol. 107 ( 2017-07), p. 117-126
    In: Neurochemistry International, Elsevier BV, Vol. 107 ( 2017-07), p. 117-126
    Materialart: Online-Ressource
    ISSN: 0197-0186
    Sprache: Englisch
    Verlag: Elsevier BV
    Publikationsdatum: 2017
    ZDB Id: 1500654-2
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 8
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 42, No. 6 ( 2011-06), p. 1757-1763
    Kurzfassung: 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.
    Materialart: Online-Ressource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Sprache: Englisch
    Verlag: Ovid Technologies (Wolters Kluwer Health)
    Publikationsdatum: 2011
    ZDB Id: 1467823-8
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 9
    Online-Ressource
    Online-Ressource
    Ovid Technologies (Wolters Kluwer Health) ; 2014
    In:  Stroke Vol. 45, No. 2 ( 2014-02), p. 614-618
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 45, No. 2 ( 2014-02), p. 614-618
    Kurzfassung: 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.
    Materialart: Online-Ressource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Sprache: Englisch
    Verlag: Ovid Technologies (Wolters Kluwer Health)
    Publikationsdatum: 2014
    ZDB Id: 1467823-8
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 10
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 48, No. 4 ( 2017-04), p. 1061-1069
    Kurzfassung: Peripheral immune cell infiltration contributes to neural injury after ischemic stroke. However, in contrast to lymphocytes and neutrophils, the role of different monocyte/macrophage subsets remains to be clarified. Therefore, we evaluated the effects of selective and unselective monocyte/macrophage depletion and proinflammatory (M1-) and anti-inflammatory (M2-) macrophage transfer on the outcome after experimental cerebral ischemia. Methods— To assess short-term effects of monocytes/macrophages in acute ischemic stroke, mice underwent transient middle cerebral artery occlusion and received either clodronate liposomes for unselective macrophage depletion, MC-21-antibody for selective depletion of proinflammatory Ly-6C high monocytes, or proinflammatory (M1-) or anti-inflammatory (M2-) macrophage transfer. In addition, the impact of MC-21-antibody administration and M2-macrophage transfer on long-term neural recovery was investigated after photothrombotic stroke. Neurobehavioral tests were used to analyze functional outcomes, infarct volumes were determined, and immunohistochemical analyses were performed to characterize the postischemic inflammatory reaction. Results— Selective and unselective monocyte/macrophage depletion and M1- and M2-macrophage transfer did not influence tissue damage and neurobehavioral outcomes in the acute phase after middle cerebral artery occlusion. Beyond, selective depletion of Ly-6C high monocytes and M2-macrophage transfer did not have an impact on neural recovery after photothrombotic stroke. Conclusions— Targeting different monocyte/macrophage subsets has no impact on outcome after ischemic stroke in mice. Altogether, our study could not identify monocytes/macrophages as relevant therapeutic targets in acute ischemic stroke.
    Materialart: Online-Ressource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Sprache: Englisch
    Verlag: Ovid Technologies (Wolters Kluwer Health)
    Publikationsdatum: 2017
    ZDB Id: 1467823-8
    Standort Signatur Einschränkungen Verfügbarkeit
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