Heppner, F L; Greter, M; Marino, D; Falsig, J; Raivich, G; Hövelmeyer, N; Waisman, A; Rülicke, T; Prinz, M; Priller, J; Becher, B; Aguzzi, A (2005). Experimental autoimmune encephalomyelitis repressed by microglial paralysis. Nature Medicine, 11(2):146-152.
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Although microglial activation occurs in inflammatory, degenerative and neoplastic central nervous system (CNS) disorders, its role in pathogenesis is unclear. We studied this question by generating CD11b-HSVTK transgenic mice, which express herpes simplex thymidine kinase in macrophages and microglia. Ganciclovir treatment of organotypic brain slice cultures derived from CD11b-HSVTK mice abolished microglial release of nitrite, proinflammatory cytokines and chemokines. Systemic ganciclovir administration to CD11b-HSVTK mice elicited hematopoietic toxicity, which was prevented by transfer of wild-type bone marrow. In bone marrow chimeras, ganciclovir blocked microglial activation in the facial nucleus upon axotomy and repressed the development of experimental autoimmune encephalomyelitis. We conclude that microglial paralysis inhibits the development and maintenance of inflammatory CNS lesions. The microglial compartment thus provides a potential therapeutic target in inflammatory CNS disorders. These results validate CD11b-HSVTK mice as a tool to study the impact of microglial activation on CNS diseases in vivo.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > University Hospital Zurich > Institute of Neuropathology|
|DDC:||570 Life sciences; biology|
610 Medicine & health
|Date:||01 February 2005|
|Deposited On:||11 Feb 2008 13:25|
|Last Modified:||27 Nov 2013 20:21|
|Publisher:||Nature Publishing Group|
|Citations:||Web of Science®. Times cited: 266|
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