Department of Neurology, Neuroscience Center, Southern Medical University Hospital of Integrated Traditional Chinese and Western Medicine, Southern Medical University, No. 13 Shi Liu Gang Road, Haizhu District, Guangzhou, 510315, China.
Department of Neurology, Neuroscience Center, Sourthern Medical University Hospital of Integrated Traditional Chinese and Western Medicine, Southern Medical University, No. 13 Shi Liu Gang Road, Haizhu District, Guangzhou, 510315, China.
Brain Behav. 2024 Jul;14(7):e3618. doi: 10.1002/brb3.3618.
High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) has been found to ameliorate cognitive impairment. However, the effects of HF-rTMS remain unknown in chronic cerebral hypoperfusion (CCH).
To investigate the effects of HF-rTMS on cognitive improvement and its potential mechanisms in CCH mice.
Daily HF-rTMS therapy was delivered after bilateral carotid stenosis (BCAS) and continued for 14 days. The mice were randomly assigned to three groups: the sham group, the model group, and the HF-rTMS group. The Y maze and the new object recognition test were used to assess cognitive function. The expressions of MAP-2, synapsis, Myelin basic protein(MBP), and brain-derived growth factors (BDNF) were analyzed by immunofluorescence staining and western blot to evaluate neuronal plasticity and white matter myelin regeneration. Nissl staining and the expression of caspase-3, Bax, and Bcl-2 were used to observe neuronal apoptosis. In addition, the activation of microglia and astrocytes were evaluated by fluorescence staining. The inflammation levels of IL-1β, IL-6, and Tumor Necrosis Factor(TNF)-α were detected by qPCR in the hippocampus of mice in each group.
Via behavioral tests, the BCAS mice showed reduced a rate of new object preference and decreased a rate of spontaneous alternations, while HF-rTMS significantly improved hippocampal learning and memory deficits. In addition, the mice in the model group showed decreased levels of MAP-2, synapsis, MBP, and BDNF, while HF-rTMS treatment reversed these effects. As expected, activated microglia and astrocytes increased in the model group, but HF-rTMS treatment suppressed these changes. HF-rTMS decreased BCAS-induced neuronal apoptosis and the expression of pro-apoptotic protein (Caspase-3 and Bax) and increased the expression of anti-apoptotic protein (Bcl-2). In addition, HF-rTMS inhibited the expression of inflammatory cytokines (IL-1β, IL-6, and TNF-α).
HF-rTMS alleviates cognitive impairment in CCH mice by enhancing neuronal plasticity and inhibiting inflammation, thus serving as a potential method for vascular cognitive impairment.
高频重复经颅磁刺激（HF-rTMS）已被发现可改善认知障碍。然而，HF-rTMS 在慢性脑低灌注（CCH）中的作用尚不清楚。
探讨 HF-rTMS 对 CCH 小鼠认知改善的影响及其潜在机制。
在双侧颈总动脉狭窄（BCAS）后每天给予 HF-rTMS 治疗，持续 14 天。将小鼠随机分为三组：假手术组、模型组和 HF-rTMS 组。使用 Y 迷宫和新物体识别试验评估认知功能。通过免疫荧光染色和 Western blot 分析 MAP-2、突触、髓鞘碱性蛋白（MBP）和脑源性生长因子（BDNF）的表达，以评估神经元可塑性和白质髓鞘再生。尼氏染色和 caspase-3、Bax 和 Bcl-2 的表达用于观察神经元凋亡。此外，通过荧光染色评估小胶质细胞和星形胶质细胞的激活。通过 qPCR 检测各组小鼠海马 IL-1β、IL-6 和 TNF-α 的炎症水平。
通过行为测试，BCAS 小鼠的新物体偏好率降低，自发交替率降低，而 HF-rTMS 显著改善了海马学习和记忆缺陷。此外，模型组小鼠 MAP-2、突触、MBP 和 BDNF 水平降低，而 HF-rTMS 治疗逆转了这些效应。如预期的那样，模型组中激活的小胶质细胞和星形胶质细胞增加，但 HF-rTMS 治疗抑制了这些变化。HF-rTMS 减少了 BCAS 诱导的神经元凋亡和促凋亡蛋白（Caspase-3 和 Bax）的表达，并增加了抗凋亡蛋白（Bcl-2）的表达。此外，HF-rTMS 抑制了炎症细胞因子（IL-1β、IL-6 和 TNF-α）的表达。
HF-rTMS 通过增强神经元可塑性和抑制炎症改善 CCH 小鼠的认知障碍，因此可能是血管性认知障碍的一种潜在治疗方法。
