TY  - JOUR
A1  - Reschke, Moritz
A1  - Salvador, Ellaine
A1  - Schlegel, Nicolas
A1  - Burek, Malgorzata
A1  - Karnati, Srikanth
A1  - Wunder, Christian
A1  - Förster, Carola Y.
T1  - Isosteviol sodium (STVNA) reduces pro-inflammatory cytokine IL-6 and GM-CSF in an in vitro murine stroke model of the blood–brain barrier (BBB)
JF  - Pharmaceutics
N2  - Early treatment with glucocorticoids could help reduce both cytotoxic and vasogenic edema, leading to improved clinical outcome after stroke. In our previous study, isosteviol sodium (STVNA) demonstrated neuroprotective effects in an in vitro stroke model, which utilizes oxygen-glucose deprivation (OGD). Herein, we tested the hypothesis that STVNA can activate glucocorticoid receptor (GR) transcriptional activity in brain microvascular endothelial cells (BMECs) as previously published for T cells. STVNA exhibited no effects on transcriptional activation of the glucocorticoid receptor, contrary to previous reports in Jurkat cells. However, similar to dexamethasone, STVNA inhibited inflammatory marker IL-6 as well as granulocyte-macrophage colony-stimulating factor (GM-CSF) secretion. Based on these results, STVNA proves to be beneficial as a possible prevention and treatment modality for brain ischemia-reperfusion injury-induced blood–brain barrier (BBB) dysfunction.
KW  - IL-6
KW  - ischemia
KW  - isosteviol sodium (STVNA)
KW  - dexamethasone
KW  - glucocorticoid receptor
KW  - cerebEND
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-286275
SN  - 1999-4923
VL  - 14
IS  - 9
ER  - 
TY  - JOUR
A1  - Rösing, Nils
A1  - Salvador, Ellaine
A1  - Güntzel, Paul
A1  - Kempe, Christoph
A1  - Burek, Malgorzata
A1  - Holzgrabe, Ulrike
A1  - Soukhoroukov, Vladimir
A1  - Wunder, Christian
A1  - Förster, Carola
T1  - Neuroprotective Effects of Isosteviol Sodium in Murine Brain Capillary Cerebellar Endothelial Cells (cerebEND) After Hypoxia
JF  - Frontiers in Cellular Neuroscience
N2  - Ischemic stroke is one of the leading causes of death worldwide. It damages neurons and other supporting cellular elements in the brain. However, the impairment is not only confined to the region of assault but the surrounding area as well. Besides, it also brings about damage to the blood-brain barrier (BBB) which in turn leads to microvascular failure and edema. Hence, this necessitates an on-going, continuous search for intervention strategies and effective treatment. Of late, the natural sweetener stevioside proved to exhibit neuroprotective effects and therapeutic benefits against cerebral ischemia-induced injury. Its injectable formulation, isosteviol sodium (STVNA) also demonstrated favorable results. Nonetheless, its effects on the BBB have not yet been investigated to date. As such, this present study was designed to assess the effects of STVNA in our in vitro stroke model of the BBB.The integrity and permeability of the BBB are governed and maintained by tight junction proteins (TJPs) such as claudin-5 and occludin. Our data show increased claudin-5 and occludin expression in oxygen and glucose (OGD)-deprived murine brain capillary cerebellar endothelial cells (cerebEND) after STVNa treatment. Likewise, the upregulation of the transmembrane protein integrin-αv was also observed. Finally, cell volume was reduced with the simultaneous administration of STVNA and OGD in cerebEND cells. In neuropathologies such as stroke, the failure of cell volume control is a major feature leading to loss of cells in the penumbra as well as adverse outcomes. Our initial findings, therefore, point to the neuroprotective effects of STVNA at the BBB in vitro, which warrant further investigation for a possible future clinical intervention.
KW  - isosteviol sodium
KW  - hypoxia
KW  - cerebEND cells
KW  - blood brain barrier
KW  - neuroprotection
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-215013
SN  - 1662-5102
VL  - 14
ER  -