Lee Yookyung, Oh Byung-Mo, Park Sung-Hye, Han Tai Ryoon
Department of Physical and Rehabilitation Medicine, Chung-Ang University Gwangmyeong Hospital, Gwangmyeong, Korea.
Department of Rehabilitation Medicine, Seoul National University College of Medicine, Seoul, Korea.
Ann Rehabil Med. 2022 Oct;46(5):228-236. doi: 10.5535/arm.22040. Epub 2022 Oct 31.
To characterize the repetitive transcranial magnetic stimulation (rTMS) induced changes in angiogenic mechanisms across different brain regions.
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).
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).
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.
描述重复经颅磁刺激(rTMS)在不同脑区诱导的血管生成机制变化。
79只成年雄性Sprague-Dawley大鼠接受大脑中动脉闭塞手术(第0天),然后对其损伤半球进行1赫兹、20赫兹刺激或假刺激,持续2周。刺激强度设定为运动阈值的100%。在第3天、第10天和第17天评估神经功能。通过组织学、免疫组织化学、蛋白质免疫印迹和实时聚合酶链反应(PCR)测定法测量梗死体积和血管生成。从缺血核心区(IC)、缺血边界区(BZ)和对侧同源皮质(CH)采集脑组织。
低频组IC中血管生成素1和突触素的光密度显著高于假刺激组(分别为p = 0.03和p = 0.03)。1赫兹rTMS显著增加了BZ中Akt磷酸化水平(与20赫兹相比,p < 0.05)。IC(与20赫兹相比,p < 0.05)、BZ(与20赫兹相比,p < 0.05)和CH(与20赫兹相比,p < 0.05;与假刺激相比,p < 0.05)中内皮型一氧化氮合酶磷酸化增加。实时PCR表明低频刺激显著增加了IC中TIE2基因的转录活性(p < 0.05)。
卒中亚急性期早期对患侧半球进行低频rTMS可促进大脑中血管生成因子和相关基因的表达,尤其是在损伤区域。