Establishment and validation of an improved in vitro model of the blood brain barrier
2009 - 2011
| Applicant: Dr. Stefan Schildknecht University of Konstanz Box M657 D-78457 Konstanz, Germany Stefan.Schildknecht@uni-konstanz.de Tel.: +49-7531-885053 |
The blood brain barrier (BBB) is an important physiological and anatomical structure, and knowledge about its function is pivotal for toxicological and pharmacological predictions. In vitro models of the BBB depend on the availability of the constituting cell types. Therefore, this project was set up to generate such cells from embryonic stem cells or by immortalization of brain cells, without further need of animal tissue or animal experimentation. Moreover, most existing barrier models address only the normal function of the BBB, but not the altered function in pathological situations. To fill this gap, the project was designed to examine inflammatory reactions of a key cell type involved in the BBB, the so-called astrocyte. This will be compared to the reactions of classical inflammatory cells of the brain, the microglia. The resulting understanding on brain inflammation, and the interaction of different brain cell types is expected to promote the understanding of complex degenerative diseases that are commonly examined in animal models, but rarely in in vitro systems Outcome: Henn A, Lund S, Hedtjärn M, Schrattenholz A, Pörzgen P, and Leist M (2009). The suitability of BV2 cells as alternative model system for primary microglia cultures or animal experiments of brain inflammation. ALTEX, 26, 83-94 Henn A, Kirner S, Leist M (2011) TLR2 hypersensitivity of astrocytes as functional consequence of their previous inflammatory activation. J Immunol 186, 3237 – 3247. Schildknecht S, Pape R, Müller R, Robotta M, Marquardt A, Bürkle A, Drescher M, Leist M (2011) Neuroprotection by minocycline caused by direct and specific scavenging of peroxynitrite. J Biol Chem, 286, 4991-5002 Christiansen SH, Schildknecht S, Selige J, Dunkern T, Rassov A, Leist M (2011) Combined anti-inflammatory effects of ß2-adrenergic agonists and PDE4 inhibitors on astrocytes by upregulation of intracellular cAMP. Neurochem Int 59, 837 - 846 Kuegler PB, Baumann BA, Zimmer B, Keller S, Marx A, Kadereit S, Leist M (2012) GFAP-independent inflammatory competence and trophic functions of astrocytes generated from murine embryonic stem cells. Glia, 60, 218-228 Schildknecht S, Kirner S, Henn A, Gasparic K, Pape R, Efremova L, Maier O, Fischer R, Leist M (2012). Characterization of Mouse Cell Line IMA2.1 as a Potential Model System to Study Astrocyte Functions. ALTEX 29, 261-274 |