Dexamethasone prevents LPS-induced microglial activation and astroglial impairment in an experimental bacterial meningitis co-culture model.
We analyzed the effect of dexamethasone on gram-negative bacteria derived lipopolysaccharide (LPS) induced inflammation in astroglial/microglial co-cultures. At the cellular level the microglial phenotype converted to an activated type after LPS incubation. Furthermore, LPS compromised functional astroglial properties like membrane resting potential, intracellular coupling and connexin 43 (Cx43) expression. This change in Cx43 expression was not due to a downregulation of Cx43 mRNA expression. Morphological and functional changes were accompanied by a time-dependent release of inflammation related cytokines. Co-incubation of dexamethasone with LPS prevented these LPS-induced changes within our glial co-culture model. The ability of dexamethasone to reconstitute astrocytic properties and to decrease microglial activation in vitro could be one possible explanation for the beneficial effects of dexamethasone in the treatment of acute bacterial meningitis in vivo.
Hinkerohe
Daniel
D
Department of Neuroanatomy and Molecular Brain Research, Ruhr- University Bochum, Universitätsstrasse 150, 44780 Bochum, Germany. hinkerohe2@freenet.de
Smikalla
Dirk
D
Schoebel
Andreas
A
Haghikia
Aiden
A
Zoidl
Georg
G
Haase
Claus G
CG
Schlegel
Uwe
U
Faustmann
Pedro M
PM
D000818:Animals; D000831:Animals, Newborn; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000166:cytology; D018920:Coculture Techniques; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D006090:Gram-Negative Bacteria / Q000737:chemistry; D007150:Immunohistochemistry; D008070:Lipopolysaccharides; D016920:Meningitis, Bacterial / Q000188:drug therapy* / Q000378:metabolism; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D000893:Anti-Inflammatory Agents; D018031:Connexin 43; D016207:Cytokines; D005938:Glucocorticoids; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D003907:Dexamethasone