Repetitive Transcranial Magnetic Stimulation Promotes Neural Stem Cell Proliferation via the Regulation of MiR-25 in a Rat Model of Focal Cerebral Ischemia

Abstract

Repetitive transcranial magnetic stimulation (rTMS) has increasingly been studied over the past decade to determine whether it has a therapeutic benefit on focal cerebral ischemia. However, the underlying mechanism of rTMS in this process remains unclear. In the current study, we investigated the effects of rTMS on the proliferation of adult neural stem cells (NSCs) and explored microRNAs (miRNAs) that were affected by rTMS. Our data showed that 10 Hz rTMS significantly increased the proliferation of adult NSCs after focal cerebral ischemia in the subventricular zone (SVZ), and the expression of miR-25 was obviously up-regulated in the ischemic cortex after rTMS. p57, an identified miR-25 target gene that regulates factors linked to NSC proliferation, was also evaluated, and it exhibited down-regulation. To further verify the role of miR-25, rats were injected with a single dose of antagomir-25 and were subjected to focal cerebral ischemia followed by rTMS treatment. The results confirmed that miR-25 could be repressed specifically and could drive the up-regulation of its target gene (p57), which resulted in the inhibition of adult NSC proliferation in the SVZ after rTMS. Thus, our studies strongly indicated that 10 Hz rTMS can promote the proliferation of adult NSCs in the SVZ after focal cerebral ischemia by regulating the miR-25/p57 pathway.

Quetiapine and repetitive transcranial magnetic stimulation ameliorate depression-like behaviors and up-regulate the proliferation of hippocampal-derived neural stem cells in a rat model of depression: The involvement of the BDNF/ERK signal pathway

“…Moreover, other studies have reported that high-frequency (25 Hz) rTMS stimulation increases the number of BrdU-positive cells in the dentate gyrus of the rat hippocampus (Ueyama et al, 2011), and our previous studies also corroborate this result (Wang et al, 2014) and therefore indicate that high-frequency rTMS can up-regulate hippocampal cell proliferation. Coincidentally recent research has found that 10 Hz rTMS for a 7-day period promotes the proliferation of adult NSCs in the subventricular zone after focal cerebral ischemia (Guo et al, 2014). Meanwhile, another research has reported that rTMS increases the proliferation of NSCs in healthy rats (Ueyama et al, 2011).…”

Neuronal differentiation of human mesenchymal stem cells in response to the domain size of graphene substrates

“…The magnetic pulses produced by the coil penetrate skull and into the brain and induce an electrical current in these regions, which depolarizes cortical and subcortical neurons . Theses properties are adopted in neurophysiology for stem cell activation and nerve cell production . In this study, rTMS (60 Hz, 300 mT) was used to induce an electrical current by magnetic field in hMSCs grown on graphene substrates characterized by different domain sizes to investigate the effects of sheet resistance on neuronal differentiation.…”

Harnessing the Potential of Biomaterials for Brain Repair after Stroke

“…Direct brain stimulation with TMS has been used to stimulate brain regions for stroke recovery (Takeuchi et al, 2005;Khedr et al, 2010) and enhance BDNF-mediated plasticity (Wang et al, 2011a). TMS has also been shown to increase the proliferation of resident adult NSCs in the SVZ though the miR-25/p57 pathway (Guo et al, 2014a). While TMS may be combined with delivery of cells or stimulation of endogenous cells, research has shown that the intensity of TMS must be finely tuned or it can negatively impact cell survival (Beom et al, 2015;Kremer et al, 2016), suggesting that more work needs to be done before this strategy can be combined successfully.…”