Biomedicine & Pharmacotherapy (Apr 2023)

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

  • Xiangxiu Chen,
  • Junshu Xue,
  • Junjie Zou,
  • Xinghong Zhao,
  • Lixia Li,
  • Renyong Jia,
  • Yuanfeng Zou,
  • Hongping Wan,
  • Yaqin Chen,
  • Xun Zhou,
  • Gang Ye,
  • Lizi Yin,
  • Xiaoxia Liang,
  • Changliang He,
  • Ling Zhao,
  • Huaqiao Tang,
  • Cheng Lv,
  • Xu Song,
  • Zhongqiong Yin

Journal volume & issue
Vol. 160
p. 114271

Abstract

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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 PRV-infected 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-α) and chemokines (CCL3, CXCL10, MCP-1), but increased the expressions of anti-inflammatory factors (IL-4, IL-10) and neurotrophic factor (TGF-β, 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.

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