Department of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, China.
Department of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, China.
Behav Brain Res. 2024 Jun 5;467:115018. doi: 10.1016/j.bbr.2024.115018. Epub 2024 Apr 27.
Poststroke cognitive impairment (PSCI) is a common complication of stroke, but effective treatments are currently lacking. Repetitive transcranial magnetic stimulation (rTMS) is gradually being applied to treat PSCI, but there is limited evidence of its efficacy. To determine rTMS effects on PSCI, we constructed a transient middle cerebral artery occlusion (tMCAO) rat model. Rats were then grouped by random digital table method: the sham group (n = 10), tMCAO group (n = 10) and rTMS group (n = 10). The shuttle box and Morris water maze (MWM) tests were conducted to detect the cognitive functions of the rats. In addition, synaptic density and synaptic ultrastructural parameters, including the active zone length, synaptic cleft width, and postsynaptic density (PSD) thickness, were quantified and analyzed using an electron microscope. What's more, synaptic associated proteins, including PSD95, SYN, and BDNF were detected by western blot. According to the shuttle box and MWM tests, rTMS improved tMCAO rats' cognitive functions, including spatial learning and memory and decision-making abilities. Electron microscopy revealed that rTMS significantly increased the synaptic density, synaptic active zone length and PSD thickness and decreased the synaptic cleft width. The western blot results showed that the expression of PSD95, SYN, and BDNF was markedly increased after rTMS stimulation. Based on these results, we propose that 20 Hz rTMS can significantly alleviate cognitive impairment after stroke. The underlying mechanism might be modulating the synaptic plasticity and up-regulating the expression PSD95, SYN, and BDNF in the hippocampus.
卒中后认知障碍（PSCI）是卒中的常见并发症，但目前缺乏有效的治疗方法。重复经颅磁刺激（rTMS）逐渐被应用于治疗 PSCI，但疗效的证据有限。为了确定 rTMS 对 PSCI 的影响，我们构建了短暂性大脑中动脉闭塞（tMCAO）大鼠模型。然后，通过随机数字表法将大鼠分为以下几组：假手术组（n=10）、tMCAO 组（n=10）和 rTMS 组（n=10）。使用穿梭箱和 Morris 水迷宫（MWM）测试检测大鼠的认知功能。此外，使用电子显微镜对突触密度和突触超微结构参数（包括活性区长度、突触间隙宽度和突触后密度（PSD）厚度）进行量化和分析。此外，通过 Western blot 检测突触相关蛋白，包括 PSD95、SYN 和 BDNF。根据穿梭箱和 MWM 测试，rTMS 改善了 tMCAO 大鼠的认知功能，包括空间学习和记忆以及决策能力。电子显微镜显示，rTMS 显著增加了突触密度、突触活性区长度和 PSD 厚度，并减少了突触间隙宽度。Western blot 结果表明，rTMS 刺激后 PSD95、SYN 和 BDNF 的表达明显增加。基于这些结果，我们提出 20 Hz rTMS 可显著减轻卒中后的认知障碍。其潜在机制可能是调节突触可塑性和上调海马中 PSD95、SYN 和 BDNF 的表达。
