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<p>Ischemic stroke is a worldwide disease with high mortality and morbidity. Kv7/KCNQ channels are key modulators of neuronal excitability and microglia function, and activation of Kv7/KCNQ channels has emerged as a potential therapeutic avenue for ischemic stroke. In the present study, we focused on a new Kv7/KCNQ channel opener QO-83 on the stroke outcomes and its therapeutic potential. Transient or distal middle cerebral artery occlusion model was established with C57 mouse to evaluate the role of QO-83. Solitary dose of QO-83 contributes to the microglia inhibition and fibrotic scar mitigation post stroke. QO83 shows prominent effect on reducing infarction area, alleviating cerebral edema, maintaining blood–brain barrier integrity, and enhancing neurogenesis. Single-nucleus RNA sequencing unveils neuroprotection and specific microglial subclusters influenced by QO-83. More importantly, QO83 shows promise in enhancing survival rates with dose dependence. Notably, these protective effects extend beyond the 4–6&#xa0;h post-reperfusion window. Additionally, continuous dosing of QO-83 correlates with enhanced cognition. In conclusion, this study highlights QO-83 as a protective agent against ischemic brain injury, showcasing its multifaceted effects and potential as a therapeutic strategy.</p>

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Neuroprotective Effects, Mechanisms of Action and Therapeutic Potential of the Kv7/KCNQ Channel Opener QO-83 in Ischemic Stroke

  • 期刊论文

  • 发表日期：

    2025年1月24日

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  • Huiran Zhang,
  • Yanfei Tian,
  • Yan Zhang,
  • Yan Wang,
  • Jinlong Qi,
  • Xiangyu Wang,
  • Yi Yuan,
  • Rong Chen,
  • Yupeng Zhao,
  • Chang Liu,
  • Najing Zhou,
  • Lanxin Liu,
  • Han Hao,
  • Xiaona Du,
  • Hailin Zhang

摘要

Ischemic stroke is a worldwide disease with high mortality and morbidity. Kv7/KCNQ channels are key modulators of neuronal excitability and microglia function, and activation of Kv7/KCNQ channels has emerged as a potential therapeutic avenue for ischemic stroke. In the present study, we focused on a new Kv7/KCNQ channel opener QO-83 on the stroke outcomes and its therapeutic potential. Transient or distal middle cerebral artery occlusion model was established with C57 mouse to evaluate the role of QO-83. Solitary dose of QO-83 contributes to the microglia inhibition and fibrotic scar mitigation post stroke. QO83 shows prominent effect on reducing infarction area, alleviating cerebral edema, maintaining blood–brain barrier integrity, and enhancing neurogenesis. Single-nucleus RNA sequencing unveils neuroprotection and specific microglial subclusters influenced by QO-83. More importantly, QO83 shows promise in enhancing survival rates with dose dependence. Notably, these protective effects extend beyond the 4–6 h post-reperfusion window. Additionally, continuous dosing of QO-83 correlates with enhanced cognition. In conclusion, this study highlights QO-83 as a protective agent against ischemic brain injury, showcasing its multifaceted effects and potential as a therapeutic strategy.