Dimethyl fumarate attenuates cerebral edema formation by protecting the blood-brain barrier integrity
Reiner Kunze, Andres Urrutia, Angelika Hoffmann, Hui Liu, Xavier Helluy, Mirko Pham, Stefan Reischl, Thomas Korff, Hugo H Marti
EXPERIMENTAL NEUROLOGY | ACADEMIC PRESS INC ELSEVIER SCIENCE | Published : 2015
Brain edema is a hallmark of various neuropathologies, but the underlying mechanisms are poorly understood. We aim to characterize how tissue hypoxia, together with oxidative stress and inflammation, leads to capillary dysfunction and breakdown of the blood-brain barrier (BBB). In a mouse stroke model we show that systemic treatment with dimethyl fumarate (DMF), an antioxidant drug clinically used for psoriasis and multiple sclerosis, significantly prevented edema formation in vivo. Indeed, DMF stabilized the BBB by preventing disruption of interendothelial tight junctions and gap formation, and decreased matrix metalloproteinase activity in brain tissue. In vitro, DMF directly sustained end..View full abstract
Awarded by Else Kroner-Fresenius-Stiftung
This work was supported by grants from B. Braun-Stiftung (HHM, RK) and Else Kroner-Fresenius-Stiftung (2012_A171; RK, HHM) and Friedrich Fischer Nachlass (University of Heidelberg; RK). The expert technical assistance of Inge Keller, Maria Harlacher and Manuel Fischer is gratefully acknowledged. We thank Laura-Ines Bohler for proofreading the manuscript.