Cho Jongwook, Lee Sangkyu, Kook Yeon Hee, Park Jiyoung, Do Heo Won, Lee C Justin, Kim Hyoung-Ihl
Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju 61005, Republic of Korea.
Center for Cognition and Sociality, Institute for Basic Science, Daejeon 34126, Republic of Korea.
Sci Adv. 2025 Jan 31;11(5):eadn7577. doi: 10.1126/sciadv.adn7577.
Stroke is caused by disruption of cerebral blood flow, leading to neuronal death and dysfunction in the interconnected areas, which results in a wide range of severe symptoms depending on the specific brain regions affected. While previous studies have primarily focused on direct modulation of neuronal activity for post-stroke treatment, accumulating evidence suggests that astrocytes may play a critical role in post-stroke progression and could serve as a potential therapeutic target for recovery. In this study, we investigate the effects of selective modulation of astrocytic calcium signals on chronic stroke using OptoSTIM1, an optogenetic tool that activates endogenous calcium channels. In contrast to channelrhodopsin-2 (ChR2), OptoSTIM1 robustly elevates astrocytic calcium levels, sustaining the increase for over 10 min upon a single activation. The calcium elevation in astrocytes in the ipsilesional sensory-parietal cortex leads to remarkable recovery from post-stroke impairment. Thus, manipulating intracellular calcium levels in astrocytes holds promise as a potential therapeutic strategy for improving recovery following a stroke.
中风是由脑血流中断引起的，导致相互连接区域的神经元死亡和功能障碍，根据受影响的特定脑区不同，会产生一系列严重症状。虽然先前的研究主要集中在中风后治疗中对神经元活动的直接调节，但越来越多的证据表明，星形胶质细胞可能在中风后的进展中起关键作用，并可能成为恢复的潜在治疗靶点。在本研究中，我们使用OptoSTIM1（一种激活内源性钙通道的光遗传学工具）研究了选择性调节星形胶质细胞钙信号对慢性中风的影响。与通道视紫红质-2（ChR2）不同，OptoSTIM1能强烈提高星形胶质细胞的钙水平，单次激活后可使钙水平升高持续超过10分钟。同侧感觉顶叶皮质星形胶质细胞内的钙升高可导致中风后损伤的显著恢复。因此，操纵星形胶质细胞内的钙水平有望成为改善中风后恢复的潜在治疗策略。
