Repetitive Transcranial Magnetic Stimulation Effects in vitro and in Animal Models

Author(s):  
Martin E. Keck
2019 ◽  
Author(s):  
Lisha Chang ◽  
Zhaowang An ◽  
Jiang Zhang ◽  
Fuling Zhou ◽  
Dali Wang ◽  
...  

Abstract Background: Cerebral ischemia is the most prevalent form of clinical stroke. Repetitive transcranial magnetic stimulation (rTMS) can modulate excitability of the cerebral cortex, and this effect is maintained after the stimulation is terminated. However, the underlying mechanisms of rTMS in cerebral ischemia remain unclear. Methods: Herein, we identified the effect of rTMS on cerebral ischemia and further explored the underlying mechanisms. An in vitro model was established using primary cultured neurons under conditions of oxygen-glucose deprivation (OGD), followed by 1 Hz or 10 Hz rTMS treatment. The levels of CREB, PKA and CaMKIV were depleted in neurons to explore the underlying regulatory mechanisms of TrkB by rTMS via CREB. A rat model of cerebral ischemia was established by middle cerebral artery occlusion (MCAO) and the rats were treated with 1 Hz or 10 Hz rTMS to investigate the effect of rTMS on neurobehavior, CREB expression, and cAMP/PKA and Ca 2+ /CaMKIV pathways. Results: rTMS was observed to promote nerve recovery ability in rats with cerebral ischemia, which was accompanied by high expression of TrkB. In OGD-treated neurons, rTMS activated CREB by upregulating cAMP/PKA and Ca 2+ /CaMKIV pathways. Moreover, rTMS induced the activation of CREB to upregulate TrkB. In MCAO rats, rTMS increased the CREB expression, enhanced cAMP, PKA and CaMKIV phosphorylation, and promoted the binding of CREB to TrkB. Conclusions: Taken together, rTMS upregulated CREB and TrkB to improve neurological function in rats with cerebral ischemia by activating cAMP/PKA and Ca 2+ /CaMKIV pathways, which could be of great significance for cerebral ischemia therapy.


Author(s):  
Alix C. Thomson ◽  
Tom A. de Graaf ◽  
Teresa Schuhmann ◽  
Gunter Kenis ◽  
Alexander T. Sack ◽  
...  

AbstractRepetitive Transcranial Magnetic Stimulation (rTMS) is an established neuromodulation technique, using electromagnetic pulses that, depending on the precise parameters, are assumed to lead to lasting neural excitability changes. rTMS has widespread applications in both research and therapy, where it has been FDA approved and is considered a first-line treatment for depression, according to recent North American and European guidelines. However, these assumed excitability effects are often difficult to replicate, and highly unreliable on the single subject/patient level. Given the increasing application of rTMS, especially in clinical practice, the absence of a method to unequivocally determine effects of rTMS on human neuronal excitability is problematic. We have taken a first step in addressing this bottleneck, by administering excitatory and inhibitory rTMS protocols, iTBS and cTBS, to a human in vitro neuron model; differentiated SH-SY5Y cells. We use live calcium imaging to assess changes in neural activity following stimulation, through quantifying fluorescence response to chemical depolarization. We found that iTBS and cTBS have opposite effects on fluorescence response; with iTBS increasing and cTBS decreasing response to chemical depolarization. Our results are promising, as they provide a clear demonstration of rTMS after-effects in a living human neuron model. We here present an in-vitro live calcium imaging setup that can be further applied to more complex human neuron models, for developing and evaluating subject/patient-specific brain stimulation protocols.


2016 ◽  
Vol 23 (1) ◽  
pp. 82-94 ◽  
Author(s):  
Alexander Tang ◽  
Gary Thickbroom ◽  
Jennifer Rodger

Since the development of transcranial magnetic stimulation (TMS) in the early 1980s, a range of repetitive TMS (rTMS) protocols are now available to modulate neuronal plasticity in clinical and non-clinical populations. However, despite the wide application of rTMS in humans, the mechanisms underlying rTMS-induced plasticity remain uncertain. Animal and in vitro models provide an adjunct method of investigating potential synaptic and non-synaptic mechanisms of rTMS-induced plasticity. This review summarizes in vitro experimental studies, in vivo studies with intact rodents, and preclinical models of selected neurological disorders—Parkinson’s disease, depression, and stroke. We suggest that these basic research findings can contribute to the understanding of how rTMS-induced plasticity can be modulated, including novel mechanisms such as neuroprotection and neurogenesis that have significant therapeutic potential.


2020 ◽  
Vol 19 (3) ◽  
pp. 220-226
Author(s):  
Chryssa Pourzitaki ◽  
Ioannis Dardalas ◽  
Frideriki Poutoglidou ◽  
Dimitrios Kouvelas ◽  
Vasilios K. Kimiskidis

Background: Repetitive Transcranial Magnetic Stimulation (rTMS) is a non-invasive brain stimulation technique that is being actively explored as a potential therapeutic modality in various neuropsychiatric disorders, such as depression, neuropathic pain, epilepsy, multiple sclerosis, and neurodegenerative disorders, including the Parkinson’s and Alzheimer’s disease. The Food and Drug Administration (FDA) approved rTMS for the treatment of major depression, migraine-associated headaches, and Obsessive Compulsive Disorder (OCD). The fact that a significant proportion of patients suffering from these disorders fail to respond to current pharmacological interventions indicates the need for alternative therapies like rTMS. Objective: The objective was to find and summarize all studies combining the use of rTMS and pharmacological interference in vitro, in order to facilitate future studies. Methods: The results of studies combining the use of rTMS with pharmacological interference in vitro were focused on. The PubMed database was searched using the terms “rTMS”, “repetitive”, “transcranial”, “magnetic”, “stimulation”, “in vitro”, “in vivo”, “cell cultures” untilMarch 2019 and 7 eligible studies were found. Results: Overall results show a synergistic effect of rTMS and pharmacotherapy in vitro with additive effectiveness, better prognosis, and superior potential management. Conclusion: The limited amount of knowledge denotes the need for additional in vitro studies on the combination of rTMS and pharmacotherapy, which could be extended to in vivo studies and ultimately help design clinical trials so as to improve the therapeutic management of patients with a wide array of neuropsychiatric disorders.


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