Resveratrol Acts Anti-Inflammatory and Neuroprotective in an Infant Rat Model of Pneumococcal Meningitis by Modulating the Hippocampal miRNome

  • Karina Barbosa de Queiroz
  • Thaís dos Santos Fontes Pereira
  • Márcio Sobreira Silva Araújo
  • Ricardo Santiago Gomez
  • Roney Santos Coimbra


Resveratrol (RSV) is anti-inflammatory and neuroprotective, cross the blood–brain barrier (BBB) and has a safe profile. Besides, RSV modulates the expression of some miRNAs related to neurological disorders. Thus, we hypothesized that RSV can be neuroprotective in pneumococcal meningitis by modulating the global microRNA expression profile (miRNome). Eleven-day old rats were intracysternally infected with S. pneumoniae (~ 2 × 106 c.f.u.) and were orally administered with RSV (50 mg/kg) or vehicle in pre-treatment (before infection) or post-treatment schedules (3 and 18 h p.i.). At 24 h p.i., animals were euthanized and apoptotic cells were counted in the hippocampal dentate gyrus of the right brain hemispheres. The hippocampi from left hemispheres were used for cytokines and chemokines multiplex assay and miRNome profiling with TaqMan OpenArray Rodent MicroRNA. Infected rats treated with RSV had lower apoptotic scores and IL-1β, CCL2, and CCL3 levels when compared to the infected group receiving placebo. Seven miRNAs were down regulated, and 18 were up regulated by pneumococcal acute meningitis. Thirty-seven miRNAs were down regulated, and three were up regulated (hsa-miR-15b-5p, hsa-miR-25-3p, hsa-miR-125b-5p) by the interaction between meningitis and RSV. Pathway enriched analysis revealed that meningitis and RSV modulate the expression of miRNAs targeting critical pathways related to the pathophysiology of bacterial meningitis. Nevertheless, hsa-miR-25-3p and hsa-miR-125b-5p target the transcription factor TEF-1, for which there are binding sites in Il-1β, Ccl 2 , and Ccl 3 genes. RSV is anti-inflammatory and neuroprotective in an infant rat model of pneumococcal meningitis and these positive effects involve the modulation of the hippocampal miRNome.


Meningitis Streptococcus pneumoniae Resveratrol Neuroprotection microRNA miRNome 


Funding Information

This work was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, 400046/2013-0), Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG, CBB – APQ-0266114), and Fundação Oswaldo Cruz (Fiocruz).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

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Authors and Affiliations

  1. 1.Imunopatologia / NeurogenômicaInstituto René Rachou, Fiocruz-MinasBelo HorizonteBrazil
  2. 2.Departamento de Cirurgia Oral e Patologia, Escola de OdontologiaUniversidade Federal de Minas GeraisBelo HorizonteBrazil
  3. 3.Grupo Integrado de Pesquisas em BiomarcadoresInstituto René Rachou, Fiocruz-MinasBelo HorizonteBrazil

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