Repetitive Transcranial Magnetic Stimulation Ameliorates Cognitive Impairment by Enhancing Neurogenesis and Suppressing Apoptosis in the Hippocampus in Rats with Ischemic Stroke

Abstract

Cognitive impairment is a serious mental deficit caused by stroke that can severely affect the quality of a survivor's life. Repetitive transcranial magnetic stimulation (rTMS) is a well-known rehabilitation modality that has been reported to exert neuroprotective effects after cerebral ischemic injury. In the present study, we evaluated the therapeutic efficacy of rTMS against post-stroke cognitive impairment (PSCI) and investigated the mechanisms underlying its effects in a middle cerebral artery occlusion (MCAO) rat model. The results showed that rTMS ameliorated cognitive deficits and tended to reduce the sizes of cerebral lesions. In addition, rTMS significantly improved cognitive function via a mechanism involving increased neurogenesis and decreased apoptosis in the ipsilateral hippocampus. Moreover, brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin-related kinase B (TrkB), were clearly upregulated in ischemic hippocampi after treatment with rTMS. Additionally, further studies demonstrated that rTMS markedly enhanced the expression of the apoptosis-related B cell lymphoma/leukemia gene 2 (Bcl-2) and decreased the expression of the Bcl-2-associated protein X (Bax) and the number of TUNEL-positive cells in the ischemic hippocampus. Both protein levels and mRNA levels were investigated. Our findings suggest that after ischemic stroke, treatment with rTMS promoted the functional recovery of cognitive impairments by inhibiting apoptosis and enhancing neurogenesis in the hippocampus and that this mechanism might be mediated by the BDNF signaling pathway.

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

“…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).…”

“…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, ).…”

“…At this stage, it is generally believed that rTMS exerts its therapeutic effect on different diseases by modulating cortical excitability and changing neurotransmitter levels in the brain. Increasing evidence indicates that rTMS regulates brain plasticity by promoting the synthesis and release of brain-derived neurotrophic factor (BDNF; Guo, Lou, Han, Deng, & Huang, 2017). rTMS also promotes the release of gamma-aminobutyric acid (GABA) in neurons (Baruth et al, 2010;Moisset, Andrade, & Bouhassira, 2016).…”

Restraint devices for repetitive transcranial magnetic stimulation in mice and rats

“…However its therapeutic mechanisms are not completely clear. Previous studies have used rodent animals to investigate its potential cellular and molecular mechanisms related to synaptic plasticity (Guo, Lou, Han, Deng, & Huang, ; Ji et al, ; Tang, Thickbroom, & Rodger, ). Unlike humans, it is not practical to keep animals (including mouse or rat) stationary during the delivery of longer rTMS period.…”

“…In previous literature, investigators used the anesthesiology method (Sasso et al, ; Sykes et al, ), or by hand (Hesselberg, Wegener, & Buchholtz, ; Lim, Lee, Yoo, & Kwon, ; Sasso et al, ), or cloth, bag and straps (Ljubisavljevic et al, ); Tang et al, ), or some undefined devices (Guo et al, ). In animals, rTMS is often used 1–2 times each day (for minutes to tens of minutes each time), lasts for a few of days or tens of days (Fleischmann & Hirschmann, ; Guo et al, ; Ji et al, ). Thus, daily anesthesia may have potentially adverse effects in animals; Restraint by hand or by cloth, bag and tape may be laborious, or be potentially inconvenient for the delivery of rTMS, especially for a longer stimulation time (over 10 min).…”