Annals of Rehabilitation Medicine

"Angiogenesis"

Original Articles

Brain disorders

Low-Frequency Repetitive Transcranial Magnetic Stimulation in the Early Subacute Phase of Stroke Enhances Angiogenic Mechanisms in Rats: Yookyung Lee, Byung-Mo Oh, Sung-Hye Park, Tai Ryoon Han; Ann Rehabil Med 2022;46(5):228-236. Published online October 31, 2022; DOI: https://doi.org/10.5535/arm.22040

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.

Citations

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Evaluation of magnetic stimulation as a non-invasive technique in treating different causes of erectile dysfunction: a prospective cohort study
Hasan El-Fakahany, Haythem Bassyouni, Sameh Fayek GamalEl Din, Mahmoud H. A. Montaser
Basic and Clinical Andrology.2025;[Epub] CrossRef
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Daniel Galimberti, Agustina Vila Echague, Ery A. Ko, Laura Pieri, Alessandra Comito, Irene Fusco, Tiziano Zingoni
Archivio Italiano di Urologia e Andrologia.2024;[Epub] CrossRef
Determining the Optimal Stimulation Sessions for TMS-Induced Recovery of Upper Extremity Motor Function Post Stroke: A Randomized Controlled Trial
Yichen Lv, Jack Jiaqi Zhang, Kui Wang, Leilei Ju, Hongying Zhang, Yuehan Zhao, Yao Pan, Jianwei Gong, Xin Wang, Kenneth N. K. Fong
Brain Sciences.2023; 13(12): 1662. CrossRef

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Effect of Magnetic Stimulation in Spinal Cord on Limb Angiogenesis and Implication: A Pilot Study: Dohong Lee, Jaewon Beom, Byung-Mo Oh, Kwan-Sik Seo; Ann Rehabil Med 2012;36(3):311-319. Published online June 30, 2012; DOI: https://doi.org/10.5535/arm.2012.36.3.311

Abstract
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Objective

To investigate the effect of repetitive magnetic stimulation (rMS) of the spinal cord on limb angiogenesis in healthy rats and explore its implication for the treatment of lymphedema.

Method

Twelve adult male Sprague-Dawley rats were divided into four groups as follows: sham rMS followed by tissue harvest 5 minutes later (group 1, n=2), 1 Hz rMS and tissue harvest 5 minutes later (group 2, n=3), 20 Hz rMS and tissue harvest 5 minutes later (group 3, n=3), 20 Hz rMS and tissue harvest 30 minutes later (group 4, n=4). Animals were treated with 20-minute rMS with 120% of the motor threshold on their left side of upper lumbar spinal cord. Expression of angiogenic factors, that is, Akt, phospho-Akt (pAkt), endothelial nitric oxide synthase (eNOS), phospho-eNOS (p-eNOS) were measured by western blot. Bilateral hindlimb muscles (quadriceps and gastrocnemius) were harvested.

Results

Expression of Akt in left quadriceps increased in group 4 compared with group 2 and 3 (3.4 and 5.3-fold each, p=0.026). Expression of eNOS in left plus right quadriceps markedly increased in group 3 and 4 compared with group 1 and 2 (p=0.007). Expressions of eNOS, Akt and p-eNOS, pAkt in gastrocnemius were not comparable between four groups (p>0.05).

Conclusion

Repetitive magnetic stimulation of the spinal cord may exert an angiogenic effect closely linked to lymphangiogenesis. It has clinical implication for the possible therapy of lymphedema caused by breast, cervical or endometrial cancer operation. Future studies with the specific lymphatic endothelial cell markers are required to confirm the effect of rMS on lymphangiogenesis.

Citations

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S A Zhivolupov, N A Rashidov, L S Onishchenko, A Yu Kravchuk, O V Kostina, E V Yakovlev, A G Trufanov
Bulletin of the Russian Military Medical Academy.2019; 21(2): 166. CrossRef
High‐Frequency Continuous Pulsed Magnetic Stimulation Does Not Adversely Affect Development on Whole Body Organs in Female Sprague–Dawley Rats
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Bao-an Pei, Jin-hua Zi, Li-sheng Wu, Cun-hua Zhang, Yun-zhen Chen
Neural Regeneration Research.2015; 10(10): 1650. CrossRef