The Differential Effects of Repetitive Magnetic Stimulation in an In Vitro Neuronal Model of Ischemia/Reperfusion Injury

被引:43
作者
Baek, Ahreum [1 ,2 ]
Kim, Ji Hyun [1 ]
Pyo, Soonil [2 ,3 ]
Jung, Joon-Ho [4 ]
Park, Eun Jee [5 ]
Kim, Sung Hoon [1 ]
Cho, Sung-Rae [2 ,3 ,6 ,7 ]
机构
[1] Yonsei Univ, Dept & Rehabil Med, Wonju Coll Med, Wonju, South Korea
[2] Yonsei Univ, Dept & Res Inst Rehabil Med, Coll Med, Seoul, South Korea
[3] Yonsei Univ, Brain Korea PLUS Project Med Sci 21, Seoul, South Korea
[4] Yonsei Univ, Dept Med, Coll Med, Seoul, South Korea
[5] Yonsei Univ, Dept Rehabil Med, Wonju Coll Med, Grad Sch, Wonju, South Korea
[6] Avison Biomed Res Ctr, Yonsei Stem Cell Ctr, Seoul, South Korea
[7] Yonsei Univ, Rehabil Inst Neuromuscular Dis, Coll Med, Seoul, South Korea
基金
新加坡国家研究基金会;
关键词
repetitive magnetic stimulation; in vitro neuronal model of ischemia/reperfusion injury; extracellular signal-regulated kinases and AKT signaling pathway; apoptosis; Ca2+-calmodulin-dependent protein kinase II cAMP-response element binding protein signaling pathway; brain-derived neurotrophic factor; synaptic plasticity; high frequency; THETA-BURST STIMULATION; LOW-FREQUENCY; UNAFFECTED HEMISPHERE; GROWTH-FACTOR; HAND FUNCTION; CELL-DEATH; EXPRESSION; PLASTICITY; SAFETY; RTMS;
D O I
10.3389/fneur.2018.00050
中图分类号
R74 [神经病学与精神病学];
学科分类号
100204 [神经病学];
摘要
Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive therapy that has been implicated in treatment of serious neurological disorders. However, the neurobiological mechanisms underlying the effects of rTMS remain unclear. Therefore, this study examined the differential effects of repetitive magnetic stimulation (rMS) in an in vitro neuronal model of ischemia/reperfusion (I/R) injury, depending on low and high frequency. Neuro-2a cells were differentiated with retinoic acid and established for in vitro neuronal model of I/R injury under a subsequent 3 h of oxygen and glucose deprivation/reoxygenation (OGD/R) condition. After the I/R injury, the differentiated neuronal cells were stimulated with rMS on day 1 and randomly divided into three groups: OGD/R+sham, OGD/R+low-frequency, and OGD/R+high-frequency groups. High-frequency rMS increases cell proliferation through activation of extracellular signal-regulated kinases and AKT-signaling pathway and inhibits apoptosis in OGD/R-injured cells. Furthermore, high-frequency rMS increases Ca2+-calmodulin-dependent protein kinase II (CaMKII)-cAMP-response element binding protein (CREB) signaling pathway, further leading to alternation of brain-derived neurotrophic factor expression and synaptic plasticity in OGD/R injured cells. These results verified the neurobiological mechanisms of frequency-dependent rMS in I/R injury-treated neuronal cells. These mechanisms will help develop more powerful and credible rTMS stimulation treatment protocols.
引用
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页数:11
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