Okabe Naohiko, Hovanesyan Mary, Azarapetian Srbui, Dai Weiye, Weisinger Batsheva, Parabucki Ana, Balter Shira Reznik, Shohami Esther, Segal Yaron, Carmichael S Thomas
Department of Neurology, David Geffen School of Medicine, UCLA, Los Angeles, CA, 90095, USA.
BrainQ Technologies, Ltd., Jerusalem, Israel.
Transl Stroke Res. 2025 Apr;16(2):194-206. doi: 10.1007/s12975-023-01202-z. Epub 2023 Nov 14.
Extremely low-frequency, low-intensity electromagnetic field (ELF-EMF) therapy is a non-invasive brain stimulation method that can modulate neuroprotection and neuroplasticity. ELF-EMF was recently shown to enhance recovery in human stroke in a small pilot clinical trial (NCT04039178). ELF-EMFs encompass a wide range of frequencies, typically ranging from 1 to 100 Hz, and their effects can vary depending on the specific frequency employed. However, whether and to what extent the effectiveness of ELF-EMFs depends on the frequency remains unclear. In the present study, we aimed to assess the efficacy of different frequency-intensity protocols of ELF-EMF in promoting functional recovery in a mouse cortical stroke model with treatment initiated 4 days after the stroke, employing a series of motor behavior tests. Our findings demonstrate that a theta-frequency ELF-EMF (5 Hz) effectively enhances functional recovery in a reach-to-grasp task, whereas neither gamma-frequency (40 Hz) nor combination frequency (5-16-40 Hz) ELF-EMFs induce a significant effect. Importantly, our histological analysis reveals that none of the ELF-EMF protocols employed in our study affect infarct volume, inflammatory, or glial activation, suggesting that the observed beneficial effects may be mediated through non-neuroprotective mechanisms. Our data indicate that ELF-EMFs have an influence on functional recovery after stroke, and this effect is contingent upon the specific frequency used. These findings underscore the critical importance of optimizing the protocol parameters to maximize the beneficial effects of ELF-EMF. Further research is warranted to elucidate the underlying mechanisms and refine the protocol parameters for optimal therapeutic outcomes in stroke rehabilitation.
极低频、低强度电磁场（ELF-EMF）疗法是一种非侵入性脑刺激方法，可调节神经保护和神经可塑性。最近在一项小型先导临床试验（NCT04039178）中发现，ELF-EMF可促进人类中风后的恢复。ELF-EMF涵盖广泛的频率范围，通常为1至100赫兹，其效果可能因所采用的特定频率而异。然而，ELF-EMF的有效性是否以及在何种程度上取决于频率仍不清楚。在本研究中，我们旨在评估ELF-EMF不同频率-强度方案对小鼠皮质中风模型功能恢复的疗效，在中风后4天开始治疗，采用一系列运动行为测试。我们的研究结果表明，θ频率的ELF-EMF（5赫兹）可有效增强抓握任务中的功能恢复，而γ频率（40赫兹）或组合频率（5-16-40赫兹）的ELF-EMF均未产生显著效果。重要的是，我们的组织学分析表明，我们研究中采用的任何ELF-EMF方案均不影响梗死体积、炎症或胶质细胞激活，这表明观察到的有益效果可能是通过非神经保护机制介导的。我们的数据表明，ELF-EMF对中风后的功能恢复有影响，且这种影响取决于所使用的特定频率。这些发现强调了优化方案参数以最大化ELF-EMF有益效果的至关重要性。有必要进行进一步研究以阐明潜在机制并完善方案参数，以实现中风康复的最佳治疗效果。
