• search hit 3 of 9
Back to Result List

The pivotal role of astrocytes in an in vitro stroke model of the blood-brain barrier

Please always quote using this URN: urn:nbn:de:bvb:20-opus-118297
  • Stabilization of the blood-brain barrier during and after stroke can lead to less adverse outcome. For elucidation of underlying mechanisms and development of novel therapeutic strategies validated in vitro disease models of the blood-brain barrier could be very helpful. To mimic in vitro stroke conditions we have established a blood-brain barrier in vitro model based on mouse cell line cerebEND and applied oxygen/glucose deprivation (OGD). The role of astrocytes in this disease model was investigated by using cell line C6. Transwell studiesStabilization of the blood-brain barrier during and after stroke can lead to less adverse outcome. For elucidation of underlying mechanisms and development of novel therapeutic strategies validated in vitro disease models of the blood-brain barrier could be very helpful. To mimic in vitro stroke conditions we have established a blood-brain barrier in vitro model based on mouse cell line cerebEND and applied oxygen/glucose deprivation (OGD). The role of astrocytes in this disease model was investigated by using cell line C6. Transwell studies pointed out that addition of astrocytes during OGD increased the barrier damage significantly in comparison to the endothelial monoculture shown by changes of transendothelial electrical resistance as well as fluorescein permeability data. Analysis on mRNA and protein levels by qPCR, western blotting and immunofluorescence microscopy of tight junction molecules claudin-3,-5,-12, occludin and ZO-1 revealed that their regulation and localisation is associated with the functional barrier breakdown. Furthermore, soluble factors of astrocytes, OGD and their combination were able to induce changes of functionality and expression of ABC-transporters Abcb1a (P-gp), Abcg2 (bcrp), and Abcc4 (mrp4). Moreover, the expression of proteases (matrixmetalloproteinases MMP-2, MMP-3, MMP-9, and t-PA) as well as of their endogenous inhibitors (TIMP-1, TIMP-3, PAI-1) was altered by astrocyte factors and OGD which resulted in significant changes of total MMP and t-PA activity. Morphological rearrangements induced by OGD and treatment with astrocyte factors were confirmed at a nanometer scale using atomic force microscopy. In conclusion, astrocytes play a major role in blood-brain barrier breakdown during OGD in vitro.show moreshow less

Download full text files

Export metadata

Additional Services

Share in Twitter Search Google Scholar Statistics
Metadaten
Author: Winfried Neuhaus, Fabian Gaiser, Anne Mahringer, Jonas Franz, Christoph Riethmüller, Carola Förster
URN:urn:nbn:de:bvb:20-opus-118297
Document Type:Journal article
Faculties:Medizinische Fakultät / Klinik und Poliklinik für Anästhesiologie (ab 2004)
Language:English
Parent Title (English):Frontiers in Cellular Neuroscience
ISSN:1662-5102
Year of Completion:2014
Volume:8
Pagenumber:352
Source:Frontiers in Cellular Neuroscience 8:352. doi:10.3389/fncel.2014.00352
DOI:https://doi.org/10.3389/fncel.2014.00352
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 612 Humanphysiologie
Tag:C6; blood-brain barrier; cerebEND; in vitro; ischemia; oxygen/glucose deprivation; stroke; traumatic brain injury
Release Date:2015/10/02
EU-Project number / Contract (GA) number:241778
OpenAIRE:OpenAIRE
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung