TY  - JOUR
A1  - Schuhmann, Michael K.
A1  - Bittner, Stefan
A1  - Meuth, Sven G.
A1  - Kleinschnitz, Christoph
A1  - Fluri, Felix
T1  - Fingolimod (FTY720-P) does not stabilize the blood-brain barrier under inflammatory conditions in an in vitro model
JF  - International Journal of Molecular Sciences
N2  - Breakdown of the blood-brain barrier (BBB) is an early hallmark of multiple sclerosis (MS), a progressive inflammatory disease of the central nervous system. Cell adhesion in the BBB is modulated by sphingosine-1-phosphate (S1P), a signaling protein, via S1P receptors (S1P\(_1\)). Fingolimod phosphate (FTY720-P) a functional S1P\(_1\) antagonist has been shown to improve the relapse rate in relapsing-remitting MS by preventing the egress of lymphocytes from lymph nodes. However, its role in modulating BBB permeabilityin particular, on the tight junction proteins occludin, claudin 5 and ZO-1has not been well elucidated to date. In the present study, FTY720-P did not change the transendothelial electrical resistance in a rat brain microvascular endothelial cell (RBMEC) culture exposed to inflammatory conditions and thus did not decrease endothelial barrier permeability. In contrast, occludin was reduced in RBMEC culture after adding FTY720-P. Additionally, FTY720-P did not alter the amount of endothelial matrix metalloproteinase (MMP)-9 and MMP-2 in RBMEC cultures. Taken together, our observations support the assumption that S1P\(_1\) plays a dual role in vascular permeability, depending on its ligand. Thus, S1P\(_1\) provides a mechanistic basis for FTY720-P-associated disruption of endothelial barrierssuch as the blood-retinal barrierwhich might result in macular edema.
KW  - randomized controlled trial
KW  - Sphingosine 1-Phosphate
KW  - vascular permeability
KW  - rat brain microvascular endothelial cell culture
KW  - tight junctions
KW  - FTY720-P
KW  - blood-brain barrier
KW  - inflammation
KW  - novo renal transplantation
KW  - endothelial cells
KW  - experimental autoimmune encephalomyelitis
KW  - relapsing multiple sclerosis
KW  - Zonula Occludens-1
KW  - matrix metalloproteinases
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-145047
VL  - 16
ER  - 
TY  - JOUR
A1  - Schuhmann, Michael K.
A1  - Fluri, Felix
T1  - Effects of fullerenols on mouse brain microvascular endothelial cells
JF  - International Journal of Molecular Sciences
N2  - Fullerenols, water-soluble C60-fullerene derivatives, have been shown to exert neuroprotective effects in vitro and in vivo, most likely due to their capability to scavenge free radicals. However, little is known about the effects of fullerenols on the blood–brain barrier (BBB), especially on cerebral endothelial cells under inflammatory conditions. Here, we investigated whether the treatment of primary mouse brain microvascular endothelial cells with fullerenols impacts basal and inflammatory blood–brain barrier (BBB) properties in vitro. While fullerenols (1, 10, and 100 µg/mL) did not change transendothelial electrical resistance under basal and inflammatory conditions, 100 µg/mL of fullerenol significantly reduced erk1/2 activation and resulted in an activation of NFκB in an inflammatory milieu. Our findings suggest that fullerenols might counteract oxidative stress via the erk1/2 and NFκB pathways, and thus are able to protect microvascular endothelial cells under inflammatory conditions.
KW  - mouse brain microvascular endothelial cell cultur
KW  - adhesion molecules
KW  - fullerenes
KW  - blood-brain barrier
KW  - inflammation
KW  - tight junctions
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158072
SN  - 1422-0067
VL  - 18
IS  - 8
ER  -