Resveratrol alleviated neuroinflammation induced by pseudorabies virus infection through regulating microglial M1/M2 polarization

Background: Pseudorabies virus (PRV) infections in susceptible non-porcine species trigger uncontrolled inflammations and eventually fatal encephalitis. Resveratrol (Res) has broad pharmacological functions including anti-virus, anti-inflammation, and neuroprotective. Purpose: We attempted to investigate the potential of Res in ameliorating PRV infection pathology in mice and decipher the mechanism of Res in treating PRV. Methods: The mice were infected by PRV to investigate the protective effect of Res. Blood-brain barrier (BBB) permeability, H&E/Nissl/TUNEL staining, Real-time PCR and ELISA analyses were performed. Primary microglia and neuron were isolated from mice and cultured. The co-culture model of microglia and neuron was established by transwell. Immunofluorescence assay and flow cytometry were used. Results: In this study, we showed that Res ameliorated brain damage by reducing BBB permeability in PRVinfected mice, and diminished the expressions of MMP-2, MMP-9 and ZO-1 in the cortex. Pathological changes of neurons by H&E/Nissl/TUNEL staining suggested that Res could alleviate neuronal lesions. Moreover, Res inhibited the expressions of pro-inflammatory factors (IL-6, TNF-alpha) and chemokines (CCL3, CXCL10, MCP-1), but increased the expressions of anti-inflammatory factors (IL-4, IL-10) and neurotrophic factor (TGF-beta, NGF and GDNF) in brain. In vitro cultured microglia cells, Res could suppress M1 microglia polarization and activate M2 microglia polarization. Co-culture of PRV-infected microglia with neuron cells by transwell system indicated that Res alleviated inflammatory response and neuronal apoptosis. Conclusion: This study provided evidence that Res could protect mice from PRV-induced encephalitis through regulation of microglia polarization and neuronal apoptosis suggesting the potential for treatment of viral encephalitis.

Automated summary

This study demonstrated that Resveratrol (Res) could protect mice from pseudorabies virus-induced encephalitis by regulating microglia polarization and neuronal apoptosis. Res reduced blood-brain barrier permeability in PRV-infected mice and decreased the expressions of MMP-2, MMP-9, and ZO-1 in the cortex. It also inhibited the expressions of pro-inflammatory factors and chemokines while increasing the expressions of anti-inflammatory factors and neurotrophic factor in the brain. In vitro experiments showed that Res suppressed M1 microglia polarization and activated M2 microglia polarization. Co-culture experiments indicated that Res alleviated inflammatory response and neuronal apoptosis.