Repetitive transcranial magnetic stimulation activates glial cells and inhibits neurogenesis after pneumococcal meningitis

PLoS One. 2020 Sep 11;15(9):e0232863. doi: 10.1371/journal.pone.0232863. eCollection 2020.

Abstract

Pneumococcal meningitis (PM) causes damage to the hippocampus, a brain structure critically involved in learning and memory. Hippocampal injury-which compromises neurofunctional outcome-occurs as apoptosis of progenitor cells and immature neurons of the hippocampal dentate granule cell layer thereby impairing the regenerative capacity of the hippocampal stem cell niche. Repetitive transcranial magnetic stimulation (rTMS) harbours the potential to modulate the proliferative activity of this neuronal stem cell niche. In this study, specific rTMS protocols-namely continuous and intermittent theta burst stimulation (cTBS and iTBS)-were applied on infant rats microbiologically cured from PM by five days of antibiotic treatment. Following two days of exposure to TBS, differential gene expression was analysed by whole transcriptome analysis using RNAseq. cTBS provoked a prominent effect in inducing differential gene expression in the cortex and the hippocampus, whereas iTBS only affect gene expression in the cortex. TBS induced polarisation of microglia and astrocytes towards an inflammatory phenotype, while reducing neurogenesis, neuroplasticity and regeneration. cTBS was further found to induce the release of pro-inflammatory cytokines in vitro. We conclude that cTBS intensified neuroinflammation after PM, which translated into increased release of pro-inflammatory mediators thereby inhibiting neuroregeneration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / cytology*
  • Astrocytes / pathology
  • Cerebellar Cortex / cytology*
  • Cerebellar Cortex / pathology
  • Cytokines / metabolism
  • Hippocampus / cytology*
  • Hippocampus / pathology
  • Male
  • Meningitis, Pneumococcal / therapy*
  • Microglia / cytology*
  • Microglia / pathology
  • Neurogenesis*
  • Rats
  • Rats, Wistar
  • Stem Cell Niche
  • Transcranial Magnetic Stimulation / adverse effects*

Substances

  • Cytokines

Grants and funding

This work was supported by a grant from the Swiss National Science Foundation (Grant 189136 to SLL). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.