High frequency repetitive transcranial magnetic stimulation improves neuronal activity without affecting astrocytes and microglia density

Zorzo, Candela; Higarza, Sara G.; Méndez, Marta; Martínez, J.A.; Pernía, Alberto M.; Árias, Jorge L.

doi:10.1016/j.brainresbull.2019.05.004

Cited by 28 publications

(14 citation statements)

References 52 publications

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“…The present rTMS is a non-invasive neuromodulation method that has been widely used in various clinical diseases in recent years, such as NP, stroke and spinal cord injury. Previous studies indicated that high-frequency rTMS (>1 Hz) could increase cortical excitability, whereas low-frequency rTMS (<1 Hz) has an inhibitory effect on neural circuits and could reduce cortical excitability (Yang & Chang, 2020;Zorzo et al, 2019). Although the mechanisms are different, both high and low frequency rTMS could effectively reduce NP (Young et al, 2014), and our study obtained the similar results.…”

Section: Discussionsupporting

confidence: 83%

Repetitive transcranial magnetic stimulation regulates neuroinflammation, relieves hyperalgesia and reverses despair‐like behaviour in chronic constriction injury rats

Zhu

et al. 2022

Eur J of Neuroscience

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Repetitive transcranial magnetic stimulation (rTMS) could effectively relieve the pain and depression in neuropathic pain (NP) patients. However, the specific treatment parameters and exact mechanism are still unclear. Our purpose is to observe the effects of rTMS on pain and despair-like behaviour in chronic constriction injury (CCI) rats and explore its possible mechanism. Thirty-two 8-week-old male Sprague-Dawley rats were randomly divided into four groups: sham operation group (S, n = 8), CCI group (n = 8), 1 Hz-rTMS group (n = 8) and 10 Hz-rTMS group (n = 8). The rTMS was applied to the left dorsal anterior agranular insular (AId) 1 week after the operation, once a day, 5 days/week for 4 consecutive weeks. Mechanical hyperalgesia, despair-like behaviours and sciatic nerve function were used to evaluate the effects of rTMS. Besides, glucose metabolism, the metabotropic glutamate receptors 5 (mGluR5), N-Methyl-D-Aspartic acid receptor type 2B (NMDAR2B), tumour necrosis factor-α (TNF-α), interleukin-6 (Ll-6) and interleukin-1β (Ll-1β) in AId were tested to explore the possible mechanism. Compared with 1 Hz-rTMS, the rats of 10 Hz-rTMS had higher the mechanical hyperalgesia, higher sugar preference and shorter swimming immobility time. Besides, the expressions of mGluR5, NMDAR2B, TNF-α, Ll-1β and Ll-6 both in 1 Hz-rTMS and 10 Hz-rTMS groups were reduced compared with the CCI group; the 10 Hz-

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Section: Discussionsupporting

confidence: 83%

Repetitive transcranial magnetic stimulation regulates neuroinflammation, relieves hyperalgesia and reverses despair‐like behaviour in chronic constriction injury rats

Zhu

et al. 2022

Eur J of Neuroscience

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“…Like the heterogeneous results after tDCS or tFUS, the exact effect of rTMS on microglia in vivo has also been largely unexplored. Candela Zorzo et al reported that 3 days of high-frequency rTMS applied in healthy rats does not alter microglia proliferation and inflammatory responses [ 58 ]. A recent study demonstrated that 5-min daily cTBS (3 pulses of 50 Hz repeated every 200 ms, intensity at 200 G) applied on the infarcted hemisphere beginning at 3 h after photothrombotic stroke injury for continuous 5-day reduced M1 phenotype microglial activation and suppressed pro-inflammatory cytokines production [ 59 ].…”

Section: Discussionmentioning

confidence: 99%

Intermittent theta-burst stimulation improves motor function by inhibiting neuronal pyroptosis and regulating microglial polarization via TLR4/NFκB/NLRP3 signaling pathway in cerebral ischemic mice

Luo

Liu

Fan

et al. 2022

J Neuroinflammation

130

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Background Neuronal pyroptosis and neuroinflammation with excess microglial activation are widely involved in the early pathological process of ischemic stroke. Repetitive transcranial magnetic stimulation (rTMS), as a non-invasive neuromodulatory technique, has recently been reported to be anti-inflammatory and regulate microglial function. However, few studies have elucidated the role and mechanism of rTMS underlying regulating neuronal pyroptosis and microglial polarization. Methods We evaluated the motor function in middle cerebral artery occlusion/reperfusion (MCAO/r) injury mice after 1-week intermittent theta-burst rTMS (iTBS) treatment in the early phase with or without depletion of microglia by colony-stimulating factor 1 receptor (CSF1R) inhibitor treatment, respectively. We further explored the morphological and molecular biological alterations associated with neuronal pyroptosis and microglial polarization via Nissl, EdU, TTC, TUNEL staining, electron microscopy, multiplex cytokine bioassays, western blot assays, immunofluorescence staining and RNA sequencing. Results ITBS significantly protected against cerebral ischemia/reperfusion (I/R) injury-induced locomotor deficits and neuronal damage, which probably relied on the regulation of innate immune and inflammatory responses, as evidenced by RNA sequencing analysis. The peak of pyroptosis was confirmed to be later than that of apoptosis during the early phase of stroke, and pyroptosis was mainly located and more severe in the peri-infarcted area compared with apoptosis. Multiplex cytokine bioassays showed that iTBS significantly ameliorated the high levels of IL-1β, IL-17A, TNF-α, IFN-γ in MCAO/r group and elevated the level of IL-10. ITBS inhibited the expression of neuronal pyroptosis-associated proteins (i.e., Caspase1, IL-1β, IL-18, ASC, GSDMD, NLRP1) in the peri-infarcted area rather than at the border of infarcted core. KEGG enrichment analysis and further studies demonstrated that iTBS significantly shifted the microglial M1/M2 phenotype balance by curbing proinflammatory M1 activation (Iba1+/CD86+) and enhancing the anti-inflammatory M2 activation (Iba1+/CD206+) in peri-infarcted area via inhibiting TLR4/NFκB/NLRP3 signaling pathway. Depletion of microglia using CSF1R inhibitor (PLX3397) eliminated the motor functional improvements after iTBS treatment. Conclusions rTMS could alleviate cerebral I/R injury induced locomotor deficits and neuronal pyroptosis by modulating the microglial polarization. It is expected that these data will provide novel insights into the mechanisms of rTMS protecting against cerebral I/R injury and potential targets underlying neuronal pyroptosis in the early phase of stroke.

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“…Prior to the conduct of the rTMS application, all animals were handled daily for 7 days in order to reduce the stress generated by the immobilization that the rTMS protocol requires. The rats were randomly assigned to five groups of different rTMS administration procedures and the protocol followed was the previously described by Zorzo et al, 2019 [33]. Briefly, the stimulation coil was placed midline with interaural coordinates 5.04 mm and bregma -3.96 mm (Fig.…”

Section: Repetitive Transcranial Magnetic Stimulation Applicationmentioning

confidence: 99%

Equipment for Repetitive Transcranial Magnetic Stimulation

Pernia

Zorzo

Prieto³

et al. 2020

IEEE Trans. Biomed. Circuits Syst.

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Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation technique used for the treatment of a great variety of neurological disorders. The technique involves applying a magnetic field in certain areas of the cerebral cortex in order to modify neuronal excitability outside the skull. However, the exact brain mechanisms underlying rTMS effects are not completely elucidated. For that purpose, and in order to generate a pulsed magnetic field, a half-bridge converter controlled by a microcontroller has been designed to apply rTMS in small animals. Moreover, the small size of the rodent head makes it necessary to design a magnetic transducer, with the aim of focusing the magnetic field on selected brain areas using a specific and a small magnetic head. Then, our purpose was to compare the effects of five different rTMS dosages on the rat brain metabolic activity. The experimental results showed that one day of stimulation leads to an enhancement of brain metabolic activity in cortical areas, meanwhile with three days of stimulation it is possible to also modify subcortical zones, results that were not found when extending the number of rTMS applications up to seven days. In consequence, the number of pulses delivered might be an important parameter in rTMS protocols, highlighting its importance in rTMS impact.

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High frequency repetitive transcranial magnetic stimulation improves neuronal activity without affecting astrocytes and microglia density

Cited by 28 publications

References 52 publications

Repetitive transcranial magnetic stimulation regulates neuroinflammation, relieves hyperalgesia and reverses despair‐like behaviour in chronic constriction injury rats

Repetitive transcranial magnetic stimulation regulates neuroinflammation, relieves hyperalgesia and reverses despair‐like behaviour in chronic constriction injury rats

Intermittent theta-burst stimulation improves motor function by inhibiting neuronal pyroptosis and regulating microglial polarization via TLR4/NFκB/NLRP3 signaling pathway in cerebral ischemic mice

Equipment for Repetitive Transcranial Magnetic Stimulation

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