High-Frequency Repetitive Transcranial Magnetic Stimulation (rTMS) Improves Functional Recovery by Enhancing Neurogenesis and Activating BDNF/TrkB Signaling in Ischemic Rats

Abstract

Repetitive transcranial magnetic stimulation (rTMS) has rapidly become an attractive therapeutic approach for stroke. However, the mechanisms underlying this remain elusive. This study aimed to investigate whether high-frequency rTMS improves functional recovery mediated by enhanced neurogenesis and activation of brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) pathway and to compare the effect of conventional 20 Hz rTMS and intermittent theta burst stimulation (iTBS) on ischemic rats. Rats after rTMS were sacrificed seven and 14 days after middle cerebral artery occlusion (MCAO), following evaluation of neurological function. Neurogenesis was measured using specific markers: Ki67, Nestin, doublecortin (DCX), NeuN and glial fibrillary acidic protein (GFAP), and the expression levels of BDNF were visualized by Western blotting and RT-PCR analysis. Both high-frequency rTMS methods significantly improved neurological function and reduced infarct volume. Moreover, 20 Hz rTMS and iTBS significantly promoted neurogenesis, shown by an increase of Ki67/DCX, Ki67/Nestin, and Ki67/NeuN-positive cells in the peri-infarct striatum. These beneficial effects were accompanied by elevated protein levels of BDNF and phosphorylated-TrkB. In conclusion, high-frequency rTMS improves functional recovery possibly by enhancing neurogenesis and activating BDNF/TrkB signaling pathway and conventional 20 Hz rTMS is better than iTBS at enhancing neurogenesis in ischemic rats.

The Effect of sequential bilateral low‐frequency rTMS over dorsolateral prefrontal cortex on serum level of BDNF and GABA in patients with primary insomnia

“…On one hand, studies on the effects of rTMS on depression and autism have shown that specific sites and frequencies of rTMS promote the release of endogenous GABA as well as reduce the loss of GABA A R on the postsynaptic membrane, thereby increasing the efficacy of GABAergic neurons (Dubin et al, ; Tan et al, ). Similarly, studies of rTMS in cognitive impairment and dyskinesia after stroke have shown that rTMS has an effect on the BDNF‐TrkB receptor pathway in the brain (Guo et al, ; Luo et al, ). On the other hand, neuroimaging and TMS measure showed cortical hyperactivity in the several types of sleep orders (Lanza, Cantone, et al, ; Lin et al, ; Nardone et al, ; Salas et al, ).…”

“…Similarly, studies of rTMS in cognitive impairment and dyskinesia after stroke have shown that rTMS has an effect on the BDNF-TrkB receptor pathway in the brain (Guo et al, 2017;Luo et al, 2017).…”

High-frequency neuronavigated rTMS effect on clinical symptoms and cognitive dysfunction: a pilot double-blind, randomized controlled study in Veterans with schizophrenia

“…Thus, the agonistic effect and upregulation of NMDA receptors by rTMS may improve the cognitive impairment. Second, a recent study showed that high-frequency rTMS may improve the impaired neuronal plasticity by activating BDNF pathway in ischemic rats 38 . Thus, highfrequency rTMS may improve cognitive deficits in SCZ patients by activation of neurotrophic factors, which play critical roles in neuroplasticity in the hippocampus related to learning and memory 39 .…”

Long Term Follow-Up Study with non-invasive brain stimulation (NBS) (rTMS and tDCS) in Parkinson’s disease (PD). Strong Age Dependency in the Effect of NBS

“…We cannot answer it directly. According to animal studies, the regeneration processes are based on the elevation of brain derived nerve factor (BDNF) (Müller et al, 2000;Cheeran et al, 2008;Antal et al, 2010) and the increased production of progenitor cells (Arias Carrión, 2008;Guo et al, 2014;Ueyama et al, 2011;Liu et al, 2015aLiu et al, , 2015bLuo et al, 2017). Stimulation with 1 Hz was compared with 30 Hz of stimulation in the brains of adult mice (Abbasnia et al, 2015).…”