Dataset Information

Low-Frequency Repetitive Transcranial Magnetic Stimulation in the Early Subacute Phase of Stroke Enhances Angiogenic Mechanisms in Rats.

ABSTRACT:

Objective

To characterize the repetitive transcranial magnetic stimulation (rTMS) induced changes in angiogenic mechanisms across different brain regions.

Methods

Seventy-nine adult male Sprague-Dawley rats were subjected to a middle cerebral artery occlusion (day 0) and then treated with 1-Hz, 20-Hz, or sham stimulation of their lesioned hemispheres for 2 weeks. The stimulation intensity was set to 100% of the motor threshold. The neurological function was assessed on days 3, 10, and 17. The infarct volume and angiogenesis were measured by histology, immunohistochemistry, Western blot, and real-time polymerase chain reaction (PCR) assays. Brain tissue was harvested from the ischemic core (IC), ischemic border zone (BZ), and contralateral homologous cortex (CH).

Results

Optical density of angiopoietin1 and synaptophysin in the IC was significantly greater in the low-frequency group than in the sham group (p=0.03 and p=0.03, respectively). The 1-Hz rTMS significantly increased the level of Akt phosphorylation in the BZ (p<0.05 vs. 20 Hz). Endothelial nitric oxide synthase phosphorylation was increased in the IC (p<0.05 vs. 20 Hz), BZ (p<0.05 vs. 20 Hz), and CH (p<0.05 vs. 20 Hz and p<0.05 vs. sham). Real-time PCR demonstrated that low-frequency stimulation significantly increased the transcriptional activity of the TIE2 gene in the IC (p<0.05).

Conclusion

Low-frequency rTMS of the ipsilesional hemisphere in the early subacute phase of stroke promotes the expression of angiogenic factors and related genes in the brain, particularly in the injured area.

SUBMITTER: Lee Y

PROVIDER: S-EPMC9650368 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Publications

Low-Frequency Repetitive Transcranial Magnetic Stimulation in the Early Subacute Phase of Stroke Enhances Angiogenic Mechanisms in Rats.

Lee Yookyung Y Oh Byung-Mo BM Park Sung-Hye SH Han Tai Ryoon TR

Annals of rehabilitation medicine 20221031 5

<h4>Objective</h4>To characterize the repetitive transcranial magnetic stimulation (rTMS) induced changes in angiogenic mechanisms across different brain regions.<h4>Methods</h4>Seventy-nine adult male Sprague-Dawley rats were subjected to a middle cerebral artery occlusion (day 0) and then treated with 1-Hz, 20-Hz, or sham stimulation of their lesioned hemispheres for 2 weeks. The stimulation intensity was set to 100% of the motor threshold. The neurological function was assessed on days 3, 10, ...[more]

PMID: 36353835

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Project description:Objectives: Either motor training or repetitive transcranial magnetic stimulation (rTMS) could modulate the neural plasticity after stroke. Therefore, synchronizing the two interventions may optimize the efficiency of recovery. In the present study, we aim to investigate the effect of rTMS along with hand grip training on the neurobehavioral and hand functional recovery in one cohort of subacute stroke patients. Methods: Thirty-nine stroke patients were enrolled in a single-center, single-blinded, randomized clinical trial. We tested different intervention effects of rTMS and hand grip training (group A), rTMS alone (group B), and hand grip training alone (group C). For the rTMS-treated groups, patients received 10 consecutive sessions of 5-Hz stimulation over the affected hemisphere with 750 pulses. Jebsen-Taylor Hand Function Test (JTHFT), Fugl-Meyer assessment of upper extremity (FMA-UE), grip strength, modified Barthel index (mBI), and ipsilesional motor evoked potential (iMEP) latency were assessed and compared across the groups. Results: We found that only rTMS along with hand grip training group all improved in JTHFT, FMA-UE, grip strength, and mBI (p ≤ 0.01) compared with the baseline among the three groups. Furthermore, this study demonstrated that rTMS plus hand grip training had much better results in improvement of neurobehavioral outcomes compared to the rTMS alone- and hand grip training alone-treated patients (p < 0.05). However, no significant differences were detected in neurophysiologic outcome between intra-groups and inter-groups (p > 0.05). Conclusion: These proof-of-concept results suggested that rTMS alone with hand grip training was a unique approach to promote hand functional recovery in stroke patients. It provided important information to design a large-scale multi-center clinical trial to further demonstrate the efficiency of the combination of central and peripheral stimulation. Clinical Trial Registration: http://www.chictr.org.cn (#ChiCTR1900023443).

Project description:JOURNAL/nrgr/04.03/01300535-202408000-00031/figure1/v/2023-12-16T180322Z/r/image-tiff Proliferation of neural stem cells is crucial for promoting neuronal regeneration and repairing cerebral infarction damage. Transcranial magnetic stimulation (TMS) has recently emerged as a tool for inducing endogenous neural stem cell regeneration, but its underlying mechanisms remain unclear. In this study, we found that repetitive TMS effectively promotes the proliferation of oxygen-glucose deprived neural stem cells. Additionally, repetitive TMS reduced the volume of cerebral infarction in a rat model of ischemic stroke caused by middle cerebral artery occlusion, improved rat cognitive function, and promoted the proliferation of neural stem cells in the ischemic penumbra. RNA-sequencing found that repetitive TMS activated the Wnt signaling pathway in the ischemic penumbra of rats with cerebral ischemia. Furthermore, PCR analysis revealed that repetitive TMS promoted AKT phosphorylation, leading to an increase in mRNA levels of cell cycle-related proteins such as Cdk2 and Cdk4. This effect was also associated with activation of the glycogen synthase kinase 3β/β-catenin signaling pathway, which ultimately promotes the proliferation of neural stem cells. Subsequently, we validated the effect of repetitive TMS on AKT phosphorylation. We found that repetitive TMS promoted Ca2+ influx into neural stem cells by activating the P2 calcium channel/calmodulin pathway, thereby promoting AKT phosphorylation and activating the glycogen synthase kinase 3β/β-catenin pathway. These findings indicate that repetitive TMS can promote the proliferation of endogenous neural stem cells through a Ca2+ influx-dependent phosphorylated AKT/glycogen synthase kinase 3β/β-catenin signaling pathway. This study has produced pioneering results on the intrinsic mechanism of repetitive TMS to promote neural function recovery after ischemic stroke. These results provide a strong scientific foundation for the clinical application of repetitive TMS. Moreover, repetitive TMS treatment may not only be an efficient and potential approach to support neurogenesis for further therapeutic applications, but also provide an effective platform for the expansion of neural stem cells.

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.

Project description:ObjectiveTo demonstrate the efficacy of high-frequency repetitive transcranial magnetic stimulation (rTMS) over the ipsilesional dorsolateral prefrontal cortex (DLPFC) on neurological recovery in patients with subacute phase stroke.MethodsPatients with supratentorial hemispheric stroke who were hospitalized for intensive rehabilitation in the subacute phase were enrolled for this retrospective analysis. Two groups of patients were selected: the rTMS group who received high-frequency (20 Hz) rTMS ≥ 5 times over the ipsilesional DLPFC, and a control group who did not receive any rTMS. The patients were further divided into groups with right- or left-side brain lesions. Functional measurements for cognitive ability, mood, speech, and activities of daily living, which were assessed at baseline and at the 1-month follow-up as a routine clinical practice, were used for analyses.ResultsAmong 270 patients with available clinical data, 133 (women, 51; age, 61.0 ± 13.8 years) met the inclusion criteria and were enrolled for analysis. There were no differences in demographic data and functional scores at baseline between the rTMS (n = 49) and control (n = 84) groups. The rTMS group showed a higher gain in the mini-mental status examination (MMSE) total score and subscores of all domains, forward digit span, and FIM-cognition than the control group (P < 0.05). Among the patients with left hemispheric lesions (n = 57), the rTMS group showed better outcomes in cognition and depression through scores of total and "attention and concentration" subscores of MMSE, FIM-cognition, and the geriatric depression scale (P < 0.05). Among the patients with right hemispheric lesions (n = 76), the rTMS group showed better outcomes in cognition through the MMSE total score and subscores of "attention and concentration," "registration," and "recall," and scores of both forward and backward digit spans (P < 0.05).ConclusionHigh-frequency rTMS over the ipsilesional DLPFC has beneficial effects on the recovery of cognition on both sides as well as mood in patients with left-sided hemispheric lesions.

Dataset Information

Low-Frequency Repetitive Transcranial Magnetic Stimulation in the Early Subacute Phase of Stroke Enhances Angiogenic Mechanisms in Rats.

Objective

Methods

Results

Conclusion

Publications

Low-Frequency Repetitive Transcranial Magnetic Stimulation in the Early Subacute Phase of Stroke Enhances Angiogenic Mechanisms in Rats.

Similar Datasets

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