Regulation of the BBB during viral encephalitis: roles of IL-12 and NOS.
Intranasal infection of mice by Vesicular Stomatitis Virus (VSV) often leads to breakdown of the blood-brain barrier (BBB). The role of Interleukin 12 (IL-12) and nitric oxide synthase (NOS) was examined here. Wild-type (WT), NOS-1 knockout (KO), and NOS-3 KO mice were infected with VSV and treated with either IL-12 or medium. IL-12 treatment of uninfected hosts did not result in pathology. In contrast with WT and NOS-1 KO mice, where extensive gross and ultrastructural correlation of BBB breakdown were evident following infection, in NOS-3 KO mice, integrity of the BBB was observed. Thus NOS-3 activity in astrocytes, endothelial cells, or ependymal cells may play an essential role in regulating the BBB.
Komatsu
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T
Department of Biology, Center for Neural Science, Kaplan Comprehensive Cancer Center, New York University, 100 Washington Square East, Mail Code 5181, New York, New York 10003-6688, USA.
Ireland
D D
DD
Chung
N
N
Doré
A
A
Yoder
M
M
Reiss
C S
CS
D000818:Animals; D001253:Astrocytes / Q000201:enzymology; D001812:Blood-Brain Barrier / Q000502:physiology*; D001921:Brain / Q000098:blood supply / Q000648:ultrastructure; D004396:Coloring Agents; D018792:Encephalitis, Viral / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000201:enzymology; D005070:Evans Blue; D017629:Gap Junctions / Q000648:ultrastructure; D007113:Immunity, Innate; D018664:Interleukin-12 / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D018353:Rhabdoviridae Infections / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology*; D013047:Specific Pathogen-Free Organisms; D014721:Vesicular stomatitis Indiana virus
D004396:Coloring Agents; D018664:Interleukin-12; D009569:Nitric Oxide; D005070:Evans Blue; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496317:Nos2 protein, mouse; C496315:Nos3 protein, mouse