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
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