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Repetitive transcranial magnetic stimulation promotes neurological functional recovery in rats with traumatic brain injury by upregulating synaptic plasticity-related proteins.

ABSTRACT: Studies have shown that repetitive transcranial magnetic stimulation (rTMS) can enhance synaptic plasticity and improve neurological dysfunction. However, the mechanism through which rTMS can improve moderate traumatic brain injury remains poorly understood. In this study, we established rat models of moderate traumatic brain injury using Feeney's weight-dropping method and treated them using rTMS. To help determine the mechanism of action, we measured levels of several important brain activity-related proteins and their mRNA. On the injured side of the brain, we found that rTMS increased the protein levels and mRNA expression of brain-derived neurotrophic factor, tropomyosin receptor kinase B, N-methyl-D-aspartic acid receptor 1, and phosphorylated cAMP response element binding protein, which are closely associated with the occurrence of long-term potentiation. rTMS also partially reversed the loss of synaptophysin after injury and promoted the remodeling of synaptic ultrastructure. These findings suggest that upregulation of synaptic plasticity-related protein expression is the mechanism through which rTMS promotes neurological function recovery after moderate traumatic brain injury.

SUBMITTER: Qian FF

PROVIDER: S-EPMC9396518 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Repetitive transcranial magnetic stimulation promotes neurological functional recovery in rats with traumatic brain injury by upregulating synaptic plasticity-related proteins.

Qian Fang-Fang FF He You-Hua YH Du Xiao-Hui XH Lu Hua-Xiang HX He Ren-Hong RH Fan Jian-Zhong JZ

Neural regeneration research 20230201 2

Studies have shown that repetitive transcranial magnetic stimulation (rTMS) can enhance synaptic plasticity and improve neurological dysfunction. However, the mechanism through which rTMS can improve moderate traumatic brain injury remains poorly understood. In this study, we established rat models of moderate traumatic brain injury using Feeney's weight-dropping method and treated them using rTMS. To help determine the mechanism of action, we measured levels of several important brain activity- ...[more]

PMID: 35900432

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Project description:Systemic inflammation is associated with alterations in complex brain functions such as learning and memory. However, diagnostic approaches to functionally assess and quantify inflammation-associated alterations in synaptic plasticity are not well-established. In previous work, we demonstrated that bacterial lipopolysaccharide (LPS)-induced systemic inflammation alters the ability of hippocampal neurons to express synaptic plasticity, i.e., the long-term potentiation (LTP) of excitatory neurotransmission. Here, we tested whether synaptic plasticity induced by repetitive magnetic stimulation (rMS), a non-invasive brain stimulation technique used in clinical practice, is affected by LPS-induced inflammation. Specifically, we explored brain tissue cultures to learn more about the direct effects of LPS on neural tissue, and we tested for the plasticity-restoring effects of the anti-inflammatory cytokine interleukin 10 (IL10). As shown previously, 10 Hz repetitive magnetic stimulation (rMS) of organotypic entorhino-hippocampal tissue cultures induced a robust increase in excitatory neurotransmission onto CA1 pyramidal neurons. Furthermore, LPS-treated tissue cultures did not express rMS-induced synaptic plasticity. Live-cell microscopy in tissue cultures prepared from a novel transgenic reporter mouse line [C57BL/6-Tg(TNFa-eGFP)] confirms that ex vivo LPS administration triggers microglial tumor necrosis factor alpha (TNFα) expression, which is ameliorated in the presence of IL10. Consistent with this observation, IL10 hampers the LPS-induced increase in TNFα, IL6, IL1β, and IFNγ and restores the ability of neurons to express rMS-induced synaptic plasticity in the presence of LPS. These findings establish organotypic tissue cultures as a suitable model for studying inflammation-induced alterations in synaptic plasticity, thus providing a biological basis for the diagnostic use of transcranial magnetic stimulation in the context of brain inflammation.

Project description:BackgroundRepetitive transcranial magnetic stimulation (rTMS) has shown promising efficacy in improving the language functions in poststroke aphasia. However, randomized controlled trials were lacking to investigate the rTMS-related neuroimaging changes underlying the therapeutic effects on language improvement in chronic aphasia.ObjectiveIn this study, we aimed to evaluate the effects of low-frequency rTMS (LF-rTMS) on chronic poststroke aphasia. We hypothesized that the deactivation of the right pars triangularis could restore the balance of interhemispheric inhibition and, hence, facilitated the functional remodeling of language networks in both the hemispheres. Furthermore, the rTMS-induced functional reorganization should underpin the language recovery after rTMS.MethodsA total of 33 patients (22 males; age: 58.70 ± 13.77 years) with chronic stroke in the left hemisphere and nonfluent aphasia were recruited in this randomized double-blinded study. The ratio of randomization between the rTMS and sham groups is 17:16. All the patients received real 1-Hz rTMS or sham stimulation (placebo coil delivered < 5% of magnetic output with similar audible click-on discharge) at the right posterior pars triangularis for 10 consecutive weekdays (stroke onset to the first stimulation: 10.97 ± 10.35 months). Functional connectivity of language networks measured by resting-state fMRI was calculated and correlated to the scores of the Concise Chinese Aphasia Test by using the stepwise regression analysis.ResultsAfter LF-rTMS intervention, significant improvement in language functions in terms of comprehension and expression abilities was observed compared with the sham group. The rTMS group showed a significant decrease of coupling strength between right pars triangularis and pars opercularis with a strengthened connection between right pars orbitalis and angular gyrus. Furthermore, the LF-rTMS significantly enhanced the coupling strength associated with left Wernicke area. Results of regression analysis showed that the identified functional remodeling involving both the hemispheres could support and predict the language recovery after LF-rTMS treatment.ConclusionWe reported the therapeutic effects of LF-rTMS and corresponding functional remodeling in chronic poststroke aphasia. Our results provided neuroimage evidence reflecting the rebalance of interhemispheric inhibition induced by LF-rTMS, which could facilitate future research in the refinement of rTMS protocol to optimize the neuromodulation efficacy and benefit the clinical management of patients with stroke.

Project description:BackgroundIt had been assumed that suppressing the undamaged contralesional motor cortex by repetitive low-frequency transcranial magnetic stimulation (rTMS) or increasing the excitability of the damaged hemisphere cortex by high-frequency rTMS will promote function recovery after stroke.ObjectivesTo assess the efficacy and safety of rTMS for improving function in people with stroke.Search methodsWe searched the Cochrane Stroke Group Trials Register (April 2012), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 4), the Chinese Stroke Trials Register (April 2012), MEDLINE (1950 to May 2012), EMBASE (1980 to May 2012), Science Citation Index (1981 to April 2012), Conference Proceedings Citation Index-Science (1990 to April 2012), CINAHL (1982 to May 2012), AMED (1985 to May 2012), PEDro (April 2012), REHABDATA (April 2012) and CIRRIE Database of International Rehabilitation Research (April 2012). In addition, we searched five Chinese databases, ongoing trials registers and relevant reference lists.Selection criteriaWe included randomised controlled trials comparing rTMS therapy with sham therapy or no therapy. We excluded trials that reported only laboratory parameters.Data collection and analysisTwo review authors independently selected trials, assessed trial quality and extracted the data. We resolved disagreements by discussion.Main resultsWe included 19 trials involving a total of 588 participants in this review. Two heterogenous trials with a total of 183 participants showed that rTMS treatment was not associated with a significant increase in the Barthel Index score (mean difference (MD) 15.92, 95% CI -2.11 to 33.95). Four trials with a total of 73 participants were not found to have a statistically significant effect on motor function (standardised mean difference (SMD) 0.51, 95% CI -0.99 to 2.01). Subgroup analyses of different stimulation frequencies or duration of illness also showed no significant difference. Few mild adverse events were observed in the rTMS groups, with the most common events being transient or mild headaches (2.4%, 8/327) and local discomfort at the site of the stimulation.Authors' conclusionsCurrent evidence does not support the routine use of rTMS for the treatment of stroke. Further trials with larger sample sizes are needed to determine a suitable rTMS protocol and the long-term functional outcome.

Dataset Information

Repetitive transcranial magnetic stimulation promotes neurological functional recovery in rats with traumatic brain injury by upregulating synaptic plasticity-related proteins.

Publications

Repetitive transcranial magnetic stimulation promotes neurological functional recovery in rats with traumatic brain injury by upregulating synaptic plasticity-related proteins.

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