Fig. 5

Sarm1 KO restores neuropathological alterations and reduces the brain inflammation induced by neurotropic viruses in mice. Eight-week-old mouse pups of wild type (WT) or Sarm1 knockout (KO) were intracranially infected with JEV, HSV-1, RABV or mock-infected. (A-C) Survival plot showing percent survival of WT and Sarm1 KO mice after JEV (A), HSV1 (B), and RABV (C) infection (n = 6 for each mock-infected; n = 18 for each neurotropic virus infection group). (D) Representative micrographs of the cerebral cortex of WT and Sarm1 KO mice infected with JEV (5 dpi), HSV-1 (5 dpi), RABV (8 dpi) or mock-infected. Red triangle: meningitis; red arrow: hemorrhage and hyperemia or perivascular cuffing; Hollow triangle: necrotic loci or neuronophagia. (E) Pathological scores of the cerebral cortex sections as shown in (D). (F) Coronal sections of the brains as shown in (D) were subjected to immunohistochemistry with NeuN antibody. Quantitative analysis of the number of NeuN⁺ cells from WT or Sarm1 KO mice. (G-I) WT and Sarm1 KO mice were infected with JEV, HSV-1, RABV or mock-infected (n = 6 for each group). At the indicated time points, levels of IFN-γ (G), TNF-α (H) and IL-6 (I) in cerebral cortex homogenates were measured by ELISA. (J) Representative micrographs of immunohistochemistry of brain sections stained for Iba-1 and GFAP from WT and Sarm1 KO surviving mice at 35 days after HSV-1 infection. (K) IFN-γ, TNF-α and IL-6 were measured with ELISA in cerebral cortex samples of WT and Sarm1 KO surviving mice with HSV-1 infection (35 dpi). All data are presented as mean ± SEM, and statistical significance was determined using Student’s t-test, one-way ANOVA was used with Tukey’s or multiple-comparison test or Log-rank (Mantel-Cox) test. *P < 0.05, **P < 0.01, ***P < 0.001. ns, not significant. ND, not detected