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Lack of functional P2X7 receptor aggravates brain edema development after middle cerebral artery occlusion

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An Erratum to this article was published on 08 November 2016

Abstract

Effective therapeutic measures against the development of brain edema, a life-threatening complication of cerebral ischemia, are necessary to improve the functional outcome for the patient. Here, we identified a beneficial role of purinergic receptor P2X7 activation in acute ischemic stroke. Involvement of P2X7 in the development of neurological deficits, infarct size, brain edema, and glial responses after ischemic cerebral infarction has been analyzed. Neurologic evaluation, magnetic resonance imaging, and immunofluorescence assays were used to characterize the receptor’s effect on the disease progress during 72 h after transient middle cerebral artery occlusion (tMCAO). Sham-operated animals were included in all experiments for control purposes. We found P2X7-deficient mice to develop a more prominent brain edema with a trend towards more severe neurological deficits 24 h after tMCAO. Infarct sizes, T2 times, and apparent diffusion coefficients did not differ significantly between wild-type and P2X7−/− animals. Our results show a characteristic spatial distribution of reactive glia cells with strongly attenuated microglia activation in P2X7−/− mice 72 h after tMCAO. Our data indicate that P2X7 exerts a role in limiting the early edema formation, possibly by modulating glial responses, and supports later microglia activation.

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Abbreviations

ADC:

Apparent diffusion coefficient

AQP4:

Aquaporin 4

CCA:

Common carotid artery

DWI:

Diffusion weighted image

ECA:

External carotid artery

ICA:

Internal carotid artery

MCA:

Middle cerebral artery

MCAO:

Middle cerebral artery occlusion

P2X7−/− :

P2X7 receptor knockout

NMR:

Nuclear magnetic resonance

pMCAO:

Permanent middle cerebral artery occlusion

RARE:

Rapid acquisition with relaxation enhancement

ROI:

Region of interest

tMCAO:

Transient middle cerebral artery occlusion

VOI:

Volume of interest

WT:

Wild-type

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Acknowledgments

This work was supported by the Deutsche Forschungsgemeinschaft (DFG) within the framework of Research Group FOR748 and TRR67 (project A6). The authors are grateful to André Rex for technical advice. Expert technical assistance and animal care were provided by Katrin Becker and Anne-Kathrin Krause.

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Authors and Affiliations

  1. Rudolf Boehm Institute of Pharmacology and Toxicology, Medical Faculty, Universität Leipzig, Härtelstr. 16-18, 04107, Leipzig, Germany

    Melanie Kaiser, Heike Franke, Ute Krügel, Wolfgang Nörenberg & Michael Schaefer

  2. Institute of Medical Physics and Biophysics, Medical Faculty, Universität Leipzig, Leipzig, Germany

    Anja Penk & Daniel Huster

Authors
  1. Melanie Kaiser
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  2. Anja Penk
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  3. Heike Franke
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  7. Michael Schaefer
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Correspondence to Michael Schaefer.

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The authors declare that they have no conflicts of interest.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution at which the studies were conducted.

Funding

This work was supported by the Deutsche Forschungsgemeinschaft (DFG) within the framework of Research Group FOR748 and TRR67 (project A6).

Additional information

An erratum to this article is available at http://dx.doi.org/10.1007/s11302-016-9523-6.

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Kaiser, M., Penk, A., Franke, H. et al. Lack of functional P2X7 receptor aggravates brain edema development after middle cerebral artery occlusion. Purinergic Signalling 12, 453–463 (2016). https://doi.org/10.1007/s11302-016-9511-x

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  • DOI: https://doi.org/10.1007/s11302-016-9511-x

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