TY  - JOUR
A1  - Fluri, Felix
A1  - Schuhmann, Michael K
A1  - Kleinschnitz, Christoph
T1  - Animal models of ischemic stroke and their application in clinical research
JF  - Drug Design, Development and Therapy
N2  - This review outlines the most frequently used rodent stroke models and discusses their strengths and shortcomings. Mimicking all aspects of human stroke in one animal model is not feasible because ischemic stroke in humans is a heterogeneous disorder with a complex pathophysiology. The transient or permanent middle cerebral artery occlusion (MCAo) model is one of the models that most closely simulate human ischemic stroke. Furthermore, this model is characterized by reliable and well-reproducible infarcts. Therefore, the MCAo model has been involved in the majority of studies that address pathophysiological processes or neuroprotective agents. Another model uses thromboembolic clots and thus is more convenient for investigating thrombolytic agents and pathophysiological processes after thrombolysis. However, for many reasons, preclinical stroke research has a low translational success rate. One factor might be the choice of stroke model. Whereas the therapeutic responsiveness of permanent focal stroke in humans declines significantly within 3 hours after stroke onset, the therapeutic window in animal models with prompt reperfusion is up to 12 hours, resulting in a much longer action time of the investigated agent. Another major problem of animal stroke models is that studies are mostly conducted in young animals without any comorbidity. These models differ from human stroke, which particularly affects elderly people who have various cerebrovascular risk factors. Choosing the most appropriate stroke model and optimizing the study design of preclinical trials might increase the translational potential of animal stroke models.
KW  - permanent and transient middle cerebral artery occlusion
KW  - thromboembolic clot model
KW  - mouse
KW  - rat
KW  - microsphere/macrosphere
KW  - endothelin-1
KW  - photothrombosis
KW  - thromboembolic stroke
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-149157
VL  - 9
ER  - 
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  - Fluri, Felix
A1  - Fleischer, Michael
A1  - Kleinschnitz, Christoph
T1  - Accidental Thrombolysis in a Stroke Patient Receiving Apixaban
JF  - Cerebrovascular Diseases Extra
N2  - No abstract available.
KW  - acute management of stroke
KW  - acute ischemic stroke
KW  - acute neurology
KW  - acute stroke imaging
KW  - acute stroke management
KW  - acute stroke outcome
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-126326
VL  - 5
ER  -