| Backgrounds: HSE is the most common non-epidemic, acute focal virus encephalitis among adults. Although aciclovir approved to be an effective drug, HSE is still a life-threatening disease with high mortality as well as significant morbidity in survivors. So far, the pathogenesis of HSE remains unclear. In HSE, the neurons are first damaged by the direct cytolytic effect of the virus after the viral infection. Then, the cell-mediated immunological responses play a predominant role in the inflammatory process and subsequent damage. After virus invasion, immunological cell produce IFN-γ,which induce iNOS synthesis in macrophages and neutrophil, resulting in a large amount of NO, which has been a reseach focus since 1980s. It is widely accepted that NO exists in many tissue and organs and has diverse biological function. However, nitric oxide synthases (NOSes) are the critical factor determining the synthesis of NO. There are at least threedifferent isoforms of NOS: neuronal, inducible and endothelial. INOS is expressed in macrophage-monocyte units. Once iNOS is induced, it is keeps catalyzing the synthesis of NO until the substrate exhausted or cell death, so a large quantity of NO is produced. It is found that NO has two paradox roles in the immunological diseases, on the one hand, it helps to fight against the many intracellular bacteria, parasites and viruses, on the other hand, it seems to participate the pathogenesis of some inflammatory diseases. Even in those researches of some neurotropic viruses in vivo or in vitro, the part of NO are Discrepancy. So far, the role of NO in HSE is no clear.Objective:To Establish a Balb/c mouse model of HSE and learn the expression of inducible nitric oxide synthase, then study the effect of AMG, an inhibitor of iNOS, on the HSE of Balb/c mice, so explore the pathogenesis of HSE.Methods: (1) 40 Balb/c mice were Intracerebrally or intranasally inoculated HSV-1 F strain 0.03 ml (titer=3.5×105/ml), another 20 mouse were mock inoculated saline as a control. The clinical and pathological changes were evaluated. By comparison, a stable HSE model was chosen. (2) 60 Mice were randomly divided into two groups. Experimental group were intracerebrally inoculated HSV-1, control group were inoculated saline. 6 mice of each group were killed at different intervals such as 2 days postinoculation (d p.i.), 5d p.i., 7d p.i.,10d p.i. and 14d p.i.. The expression of iNOS mRNA of the brains was detected by RT-PCR, at the same time, glyceraldehyde-3-phosphate dehydrogenase (GAPD) was used as an internal control for RNA isolating and procedures of RT-PCR. PCR products were resolved in 1.2% agarose gel and were semi-quantity analyzed. Furthermore, some mice were treated with aminoguanidine (AMG), a specific inhibitor of iNOS, or saline or nothing, and the clinic, morbidity and mortality were evaluated.Results: (1)Animals intracerebrally inoculated HSV-1 exhibited different symptoms such as hair disorder, downcast, agitation, seizure and death, etc. Mice showed clinical feature as early as 3d p.i., which reached peak at 7～10d p.i. and recovered about 14d p.i., some mice were dead at 6～10d p.i.. About 85% mice had clinical symptoms and mortality was 25% approximately. Pathological changes included inflammatory cell infiltration of meninges and parenchyma, neurons necrosis, lymphocytic muff around the vessel and microglia proliferation, etc. Mice of intranasal inoculation group didn't show apparent clinical changes but some mild histological evidence was found. Mock inoculation mice kept alive without any symptom or death. (2)The iNOS mRNA expression in the brain of infectious mouse could be detected as early as 2d p.i., reached peak at 10d p.i. and decreased rapidly at 14d p.i., but didn't return to the base line. On the contrary, noiNOS mRNA was found in the brain of control mice. (3) The morbidity decreased to 40% after treated with AMG, treated mice were all alive. There was a significant difference between AMG group and non-treatment group; however...
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