Cai Ying, Qiu Baoshan, Liao Mengshi, Liu Xiaolu, Lin Jing, Lan Linfang, Xu Guangqing, Fan Yuhua
Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, No. 58 Zhongshan Road 2, Guangzhou 510080, China.
Department of Rehabilitation Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China; China National Clinical Research Center for Neurological Diseases, Beijing 100050, China.
Neuroscience. 2020 Jun 15;437:98-106. doi: 10.1016/j.neuroscience.2020.04.029. Epub 2020 Apr 27.
We investigated whether intermittent theta burst stimulation (iTBS) can improve the spatial cognitive function of rats with hypertension-induced cerebral small vessel disease. To prove our hypothesis, stroke-prone renovascular hypertensive rats (RHRSPs) were treated with iTBS beginning at postoperative week 22. The Morris water maze was performed to assess spatial cognitive function. The expression of the N-methyl-d-aspartate receptor (NMDAR) subunits NR1, NR2A and NR2B, calcium/calmodulin-dependent protein kinase IIα (CaMKIIα), p-CaMKIIα and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunit 1 (GluR1) in the hippocampus were evaluated by western blot analysis. The distribution of GluR1, glial fibrillary acidic protein (GFAP) and ionized calcium-binding adaptor molecule-1 (IBa-1) in the CA1 and CA3 regions and dentate gyrus (DG) of the hippocampus were evaluated by immunofluorescence analysis. Treatment with iTBS significantly improved the spatial cognitive function of RHRSPs, increased the expression of NR2B, p-CaMKIIα and GluR1 in the hippocampus, and decreased the proliferation of astrocytes and microglia. Our results showed that iTBS treatment had a beneficial effect on the cognitive impairments induced by cerebral small vessel disease, potentially through the activation of the NR2B-CaMKII pathway, an increase in GluR1 expression and the suppression of astrocyte and microglial activation.
我们研究了间歇性θ波爆发刺激（iTBS）是否能改善高血压性脑小血管病大鼠的空间认知功能。为了验证我们的假设，从术后第22周开始对易卒中型肾血管性高血压大鼠（RHRSPs）进行iTBS治疗。采用莫里斯水迷宫评估空间认知功能。通过蛋白质免疫印迹分析评估海马中N-甲基-D-天冬氨酸受体（NMDAR）亚基NR1、NR2A和NR2B、钙/钙调蛋白依赖性蛋白激酶IIα（CaMKIIα）、磷酸化CaMKIIα（p-CaMKIIα）和α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体亚基1（GluR1）的表达。通过免疫荧光分析评估海马CA1和CA3区以及齿状回（DG）中GluR1、胶质纤维酸性蛋白（GFAP）和离子钙结合衔接分子1（IBa-1）的分布。iTBS治疗显著改善了RHRSPs的空间认知功能，增加了海马中NR2B、p-CaMKIIα和GluR1的表达，并减少了星形胶质细胞和小胶质细胞的增殖。我们的结果表明，iTBS治疗对脑小血管病引起的认知障碍具有有益作用，可能是通过激活NR2B-CaMKII途径、增加GluR1表达以及抑制星形胶质细胞和小胶质细胞的激活来实现的。
