scholarly journals Transcranial Magnetic stimulation (TMS) modulates functional activity of SH-SY5Y cells: An in vitro model provides support for assumed excitability changes

2020 ◽  
Author(s):  
Alix C. Thomson ◽  
Tom A. de Graaf ◽  
Teresa Schuhmann ◽  
Gunter Kenis ◽  
Alexander T. Sack ◽  
...  
Keyword(s):  
Transcranial Magnetic Stimulation ◽  
Calcium Imaging ◽  
Magnetic Stimulation ◽  
Neuron Model ◽  
Repetitive Transcranial Magnetic Stimulation ◽  
Patient Specific ◽  
Single Subject ◽  
Fluorescence Response ◽  
Human Neuron

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.

scholarly journals Repetitive Transcranial Magnetic Stimulation Promotes Neural Stem Cell Proliferation and Differentiation after Intracerebral Hemorrhage in Mice*

2019 ◽  
Vol 28 (5) ◽  
pp. 568-584 ◽  
Author(s):  
Mengchu Cui ◽  
Hongfei Ge ◽  
Han Zeng ◽  
Hongxiang Yan ◽  
Le Zhang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Neuronal Differentiation ◽  
Calcium Imaging ◽  
Magnetic Stimulation ◽  
Repetitive Transcranial Magnetic Stimulation ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Physical Treatment ◽  
Proliferation And Differentiation

Repetitive transcranial magnetic stimulation (rTMS) is a physical treatment applied during recovery after intracerebral hemorrhage (ICH). With in vivo and in vitro assays, the present study sought to investigate how rTMS influences neural stem cells (NSCs) after ICH and the possible mechanism. Following a collagenase-induced ICH, adult male C57BL/6 J mice were subjected to rTMS treatment every 24 h for 5 days using the following parameters: frequency, 10 Hz; duration, 2 s; wait time, 5.5 s; 960 trains (500 µV/div, 5 ms/div, default setting). Brain water content and neurobehavioral score were assessed at days 1, 3, and 5 after ICH. The proliferation and differentiation of NSCs were observed using immunofluorescence staining for Nestin, Ki-67, DCX, and GFAP on day 3 after ICH, and rTMS treatment with the same parameters was applied to NSCs in vitro. We found that rTMS significantly reduced brain edema and alleviated neural functional deficits. The mice that underwent ICH recovered faster after rTMS treatment, with apparent proliferation and neuronal differentiation of NSCs and attenuation of glial differentiation and GFAP aggregation. Accordingly, proliferation and neuronal differentiation of isolated NSCs were promoted, while glial differentiation was reduced. In addition, microarray analysis, western blotting assays, and calcium imaging were applied to initially investigate the potential mechanism. Bioinformatics showed that the positive effect of rTMS on NSCs after ICH was largely related to the MAPK signaling pathway, which might be a potential hub signaling pathway under the complex effect exerted by rTMS. The results of the microarray data analysis also revealed that Ca2+ might be the connection between physical treatment and the MAPK signaling pathway. These predictions were further identified by western blotting analysis and calcium imaging. Taken together, our findings showed that rTMS after ICH exhibited a restorative effect by enhancing the proliferation and neuronal differentiation of NSCs, potentially through the MAPK signaling pathway.

scholarly journals Repetitive transcranial magnetic stimulation improves neurological function after cerebral ischemia in rats by increasing CREB-regulated TrkB via activation of cAMP/PKA and Ca2+/CaMKIV signaling pathways

2019 ◽  
Author(s):  
Lisha Chang ◽  
Zhaowang An ◽  
Jiang Zhang ◽  
Fuling Zhou ◽  
Dali Wang ◽  
...  
Keyword(s):  
Transcranial Magnetic Stimulation ◽  
Cerebral Ischemia ◽  
Magnetic Stimulation ◽  
Repetitive Transcranial Magnetic Stimulation ◽  
Glucose Deprivation ◽  
Artery Occlusion ◽  
Neurological Function ◽  
Nerve Recovery ◽  
Underlying Mechanisms

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.

scholarly journals The Effectiveness of Transcranial Magnetic Stimulation (TMS) Paradigms as Treatment Options for Recovery of Language Deficits in Chronic Poststroke Aphasia

2022 ◽  
Vol 2022 ◽  
pp. 1-25
Author(s):  
Anastasios M. Georgiou ◽  
Maria Kambanaros
Keyword(s):  
Transcranial Magnetic Stimulation ◽  
Magnetic Stimulation ◽  
Repetitive Transcranial Magnetic Stimulation ◽  
Treatment Options ◽  
Receptive Language ◽  
Single Subject ◽  
Language Therapy ◽  
Noninvasive Methods ◽  
The Right

Background. In an effort to boost aphasia recovery, modern rehabilitation, in addition to speech and language therapy (SALT), is increasingly incorporating noninvasive methods of brain stimulation. The present study is aimed at investigating the effectiveness of two paradigms of neuronavigated repetitive transcranial magnetic stimulation (rTMS): (i) 1 Hz rTMS and (ii) continuous theta burst stimulation (cTBS) each as a standalone treatment for chronic aphasia poststroke. Methods. A single subject experimental design (SSED) trial was carried out in which six people with aphasia (PWA) were recruited, following a single left hemispheric stroke more than six months prior to the study. Three individuals were treated with 1 Hz rTMS, and the remaining three were treated with cTBS. In all cases, TMS was applied over the right pars triangularis (pTr). Language assessment, with standardized and functional measures, and cognitive evaluations were carried out at four time points: twice prior to treatment (baseline), one day immediately posttreatment, and at follow-up two months after treatment was terminated. Quality of life (QoL) was also assessed at baseline and two months posttreatment. In addition, one of the participants with severe global aphasia was followed up again one and two years posttherapy. Results. For all participants, both rTMS paradigms (1 Hz rTMS and cTBS) generated trends towards improvement in several language skills (i.e., verbal receptive language, expressive language, and naming and reading) one day after treatment and/or two months after therapy. Rated QoL remained stable in three individuals, but for the other three, the communication scores of the QoL were reduced, while two of them also showed a decline in the psychological scores. The participant that was treated with cTBS and followed for up to two years showed that the significant improvement she had initially exhibited in comprehension and reading skills two months after TMS (1st follow-up) was sustained for at least up to two years. Conclusion. From the current findings, it is suggested that inhibitory TMS over the right pTr has the potential to drive neuroplastic changes as a standalone treatment that facilitates language recovery in poststroke aphasia.

Repetitive Transcranial Magnetic Stimulation of the Brain

2016 ◽  
Vol 23 (1) ◽  
pp. 82-94 ◽  
Author(s):  
Alexander Tang ◽  
Gary Thickbroom ◽  
Jennifer Rodger
Keyword(s):  
Transcranial Magnetic Stimulation ◽  
Magnetic Stimulation ◽  
Therapeutic Potential ◽  
Repetitive Transcranial Magnetic Stimulation ◽  
Experimental Studies ◽  
Basic Research ◽  
In Vitro Models ◽  
In Vivo Studies

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.

The Combination of rTMS and Pharmacotherapy on In Vitro Models: A Mini-Review

2020 ◽  
Vol 19 (3) ◽  
pp. 220-226
Author(s):  
Chryssa Pourzitaki ◽  
Ioannis Dardalas ◽  
Frideriki Poutoglidou ◽  
Dimitrios Kouvelas ◽  
Vasilios K. Kimiskidis
Keyword(s):  
Transcranial Magnetic Stimulation ◽  
Magnetic Stimulation ◽  
Repetitive Transcranial Magnetic Stimulation ◽  
Significant Proportion ◽  
Neuropsychiatric Disorders ◽  
Therapeutic Modality ◽  
Compulsive Disorder ◽  
Pubmed Database

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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