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

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.

Microglia mediate synaptic plasticity induced by 10 Hz repetitive transcranial magnetic stimulation

“…Considering their role in pathological brain states (Graeber and Streit, 2010; Prinz et al, 2019; Prinz et al, 2021), it is interesting to theorize that the therapeutic effects of rTMS could—at least in part—depend on the modulation of microglia function. Indeed, evidence has been provided that rTMS affects microglial markers (Clarke et al, 2017; Cullen and Young, 2016; Li et al, 2021; Muri et al, 2020; Stevanovic et al, 2019). However, direct experimental evidence determining the role of microglia in rTMS-induced neural plasticity is currently not available.…”

Intermittent theta-burst stimulation improves motor function by inhibiting neuronal pyroptosis and regulating microglial polarization via TLR4/NFκB/NLRP3 signaling pathway in cerebral ischemic mice

“…A recent study demonstrated that 5-min daily cTBS (3 pulses of 50 Hz repeated every 200 ms, intensity at 200 G) applied on the infarcted hemisphere beginning at 3 h after photothrombotic stroke injury for continuous 5-day reduced M1 phenotype microglial activation and suppressed pro-inflammatory cytokines production [ 59 ]. In contrast, Lukas Muri et al reported that cTBS (three 30 Hz pulses repeated at intervals of 100 ms for 200 times) increased abundance of CD68 + cells (M1 phenotype) in cerebral cortex and hippocampal dentate gyrus [ 60 ]. Indeed, our present data set provided further evidence in this regard.…”

Microglial Cytokines Mediate Plasticity Induced by 10 Hz Repetitive Magnetic Stimulation

“…Considering their role in pathologic brain states (Graeber and Streit, 2010;Prinz et al, 2019Prinz et al, , 2021, it is interesting to theorize that the therapeutic effects of rTMS could, at least in part, depend on the modulation of microglia function. Indeed, evidence has been provided that rTMS affects microglial markers (Cullen and Young, 2016;Clarke et al, 2017;Stevanovic et al, 2019;Muri et al, 2020;Li et al, 2021). However, direct experimental evidence determining the role of microglia in rTMS-induced neural plasticity is currently not available.…”