Department of Neurology, Emory University, Atlanta, Georgia, USA.
Department of Rehabilitation Medicine, Emory University, Atlanta, Georgia, USA.
Ann Neurol. 2023 Feb;93(2):336-347. doi: 10.1002/ana.26509. Epub 2022 Oct 8.
Stroke is a leading cause of human death and disability. Effective early treatments with reasonable therapeutic windows remain critically important to improve the outcomes of stroke. Transcranial magnetic stimulation (TMS) is an established noninvasive technique that has been applied clinically and in animal research for multiple brain disorders, but few studies have examined acute neuroprotection against ischemic stroke. The present investigation tested the novel approach of low-frequency repetitive TMS (rTMS) as an acute treatment after ischemic stroke.
Adult male rats received focal ischemic surgery through occlusion of the right middle cerebral artery for 60 minutes. The rats received either rTMS or sham treatment with 1.5-, 3-, 4-, or 7-hour delay after the onset of stroke. Low-frequency and low-intensity rTMS was applied to the rat brain for two 30-minute episodes separated by a 1-hour interval.
Three days after stroke, compared to stroke controls, rats receiving rTMS treatment with a 1.5-hour delay showed a 35% reduction of infarct volume. Protective effects were also seen with 3- or 4-hour-delayed treatments by rTMS, shown as reduced infarct volume and cell death. rTMS treatment upregulated the antiapoptotic factor Bcl-2 and downregulated the proapoptotic caspase-3 cleavage, expressions of Bax and matrix metallopeptidase-9. In sensorimotor functional assessments 3 to 21 days after stroke, rats receiving rTMS treatment with a 1.5- or 3-hour delay showed significantly better performance compared to stroke controls.
These results support the inference that low-frequency rTMS may be feasible as a neuroprotective acute treatment after ischemic stroke. ANN NEUROL 2023;93:336-347.
中风是人类死亡和残疾的主要原因。在合理的治疗窗口内，有效的早期治疗对于改善中风患者的预后仍然至关重要。经颅磁刺激（TMS）是一种成熟的非侵入性技术，已在多种脑部疾病的临床和动物研究中得到应用，但很少有研究探讨其对缺血性中风的急性神经保护作用。本研究测试了低频重复经颅磁刺激（rTMS）作为缺血性中风后急性治疗的新方法。
成年雄性大鼠通过阻断右侧大脑中动脉 60 分钟进行局灶性缺血性手术。大鼠在中风发作后 1.5、3、4 或 7 小时分别接受 rTMS 或假处理。低频和低强度 rTMS 应用于大鼠大脑，两次 30 分钟的发作之间间隔 1 小时。
中风后 3 天，与中风对照组相比，1.5 小时延迟接受 rTMS 治疗的大鼠梗死体积减少了 35%。3 或 4 小时延迟 rTMS 治疗也显示出保护作用，表现为梗死体积和细胞死亡减少。rTMS 治疗上调了抗凋亡因子 Bcl-2，并下调了促凋亡 caspase-3 裂解、Bax 和基质金属蛋白酶-9 的表达。中风后 3 至 21 天进行感觉运动功能评估时，与中风对照组相比，1.5 或 3 小时延迟接受 rTMS 治疗的大鼠表现出明显更好的性能。
这些结果支持低频 rTMS 作为缺血性中风后神经保护急性治疗的可行性推断。神经病学年鉴 2023；93：336-347。
