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Volume 22
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10.3390/ijms22189893
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Article

Treatment with Edoxaban Attenuates Acute Stroke Severity in Mice by Reducing Blood–Brain Barrier Damage and Inflammation

by
Michael Bieber
1,
Kathrin I. Foerster
2,
Walter E. Haefeli
2,
Mirko Pham
3,
Michael K. Schuhmann
1 and
Peter Kraft
1,4,*
1
Department of Neurology, University Hospital Würzburg, 97080 Würzburg, Germany
2
Department of Clinical Pharmacology and Pharmacoepidemiology, Heidelberg University Hospital, 69120 Heidelberg, Germany
3
Department of Neuroradiology, University Hospital Würzburg, 97080 Würzburg, Germany
4
Department of Neurology, Klinikum Main-Spessart, 97816 Lohr, Germany
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2021, 22(18), 9893; https://doi.org/10.3390/ijms22189893
Submission received: 5 August 2021 / Revised: 8 September 2021 / Accepted: 10 September 2021 / Published: 13 September 2021
(This article belongs to the Special Issue Cellular and Molecular Targets in Acute Ischemic Stroke)
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Abstract

Patients with atrial fibrillation and previous ischemic stroke (IS) are at increased risk of cerebrovascular events despite anticoagulation. In these patients, treatment with non-vitamin K oral anticoagulants (NOAC) such as edoxaban reduced the probability and severity of further IS without increasing the risk of major bleeding. However, the detailed protective mechanism of edoxaban has not yet been investigated in a model of ischemia/reperfusion injury. Therefore, in the current study we aimed to assess in a clinically relevant setting whether treatment with edoxaban attenuates stroke severity, and whether edoxaban has an impact on the local cerebral inflammatory response and blood–brain barrier (BBB) function after experimental IS in mice. Focal cerebral ischemia was induced by transient middle cerebral artery occlusion in male mice receiving edoxaban, phenprocoumon or vehicle. Infarct volumes, functional outcome and the occurrence of intracerebral hemorrhage were assessed. BBB damage and the extent of local inflammatory response were determined. Treatment with edoxaban significantly reduced infarct volumes and improved neurological outcome and BBB function on day 1 and attenuated brain tissue inflammation. In summary, our study provides evidence that edoxaban might exert its protective effect in human IS by modulating different key steps of IS pathophysiology, but further studies are warranted.
Keywords: edoxaban; thrombo-inflammation; blood–brain barrier; tMCAO; experimental stroke; hemorrhagic transformation; NOAC edoxaban; thrombo-inflammation; blood–brain barrier; tMCAO; experimental stroke; hemorrhagic transformation; NOAC

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MDPI and ACS Style

Bieber, M.; Foerster, K.I.; Haefeli, W.E.; Pham, M.; Schuhmann, M.K.; Kraft, P. Treatment with Edoxaban Attenuates Acute Stroke Severity in Mice by Reducing Blood–Brain Barrier Damage and Inflammation. Int. J. Mol. Sci. 2021, 22, 9893. https://doi.org/10.3390/ijms22189893

AMA Style

Bieber M, Foerster KI, Haefeli WE, Pham M, Schuhmann MK, Kraft P. Treatment with Edoxaban Attenuates Acute Stroke Severity in Mice by Reducing Blood–Brain Barrier Damage and Inflammation. International Journal of Molecular Sciences. 2021; 22(18):9893. https://doi.org/10.3390/ijms22189893

Chicago/Turabian Style

Bieber, Michael, Kathrin I. Foerster, Walter E. Haefeli, Mirko Pham, Michael K. Schuhmann, and Peter Kraft. 2021. "Treatment with Edoxaban Attenuates Acute Stroke Severity in Mice by Reducing Blood–Brain Barrier Damage and Inflammation" International Journal of Molecular Sciences 22, no. 18: 9893. https://doi.org/10.3390/ijms22189893

APA Style

Bieber, M., Foerster, K. I., Haefeli, W. E., Pham, M., Schuhmann, M. K., & Kraft, P. (2021). Treatment with Edoxaban Attenuates Acute Stroke Severity in Mice by Reducing Blood–Brain Barrier Damage and Inflammation. International Journal of Molecular Sciences, 22(18), 9893. https://doi.org/10.3390/ijms22189893

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