A Time-dependent Glia cell-Mediated Neuroprotective Effects of Kv7/KCNQ channel opener QO-83 in Ischemic Stroke: Mechanisms of Action and Therapeutic Potential

This study investigates the protective role of Kv7 channel opener QO-83 in mouse brain injury induced by ischemia-reperfusion and permanent ischemia. QO-83 shows promise in enhancing survival rates, reducing infarction area, cerebral edema, and maintaining the blood-brain barrier. Furthermore, QO-83 administration correlates with enhanced cognition, memory, and fibrotic scar mitigation. Notably, these protective effects extend beyond the 4-6-hour post-reperfusion window. Single-nucleus RNA sequencing unveils distinct microglial and astrocyte clusters influenced by QO-83, potentially mediated via KCNQ3/5 targets. Notably, QO-83's influence on nestin-positive cell differentiation underscores its potential in limiting fibrotic scar formation. This study highlights QO-83 as a protective agent against ischemic brain injury, showcasing its multifaceted effects and potential as a therapeutic strategy. Overall design: C57 wide type mice were subjected to 90 min middle cerebral artery occlusion and then reperfusion. 3 days later, ischemic brains were collected from 1 sham mouse, 2 model-ßCD mice and 2 model-QO-83 mice and analyzed using single-nuclear RNA sequencing.