Experimental herpes simplex virus encephalitis: inhibition of the expression of inducible nitric oxide synthase in mouse brain tissue.
In the brain tissue of 36 mice infected with herpes simplex virus type 1, strain F, we determined the expression of inducible nitric oxide synthase (iNOS) with semiquantitative reverse transcription polymerase chain reaction. The viral burden was quantitated by polymerase chain reaction. Nitric oxide, induced by iNOS, may contribute to neuronal cell damage following virus infection. As the experimental therapeutic strategy in herpes simplex virus encephalitis (HSVE), we used: N-nitro-L-arginin (L-NA), a selective inhibitor of iNOS; and combination therapies of either methylprednisolone/acyclovir or L-NA/acyclovir. The viral burden peaked in acute disease, and then returned to a low baseline value, except in untreated controls. The expression of iNOS mRNA was suppressed by L-NA and by acyclovir/corticosteroids. INOS inhibition may provide an additional therapeutic strategy targeted specifically to suppress iNOS expression as a potential secondary mechanism of tissue damage in acute and chronic HSVE.
Meyding-Lamadé
Uta
U
Department of Neurology, University of Heidelberg, Heidelberg, Germany. uta_meyding-lamade@med.uni-heidelberg.de
Seyfer
Sonja
S
Haas
Jürgen
J
Dvorak
Florian
F
Kehm
Roland
R
Lamadé
Wolfram
W
Hacke
Werner
W
Wildemann
Brigitte
B
D000212:Acyclovir / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D001921:Brain / Q000201:enzymology* / Q000821:virology; D004359:Drug Therapy, Combination; D020803:Encephalitis, Herpes Simplex / Q000188:drug therapy / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D018259:Herpesvirus 1, Human; D008775:Methylprednisolone / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D018696:Neuroprotective Agents / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000235:genetics*; D052247:Nitric Oxide Synthase Type II; D019335:Nitroarginine / Q000494:pharmacology; D019562:Viral Load
D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D018696:Neuroprotective Agents; D019335:Nitroarginine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D000212:Acyclovir; D008775:Methylprednisolone