Studies on poly-ICLC treatment as a potent neuroprotective therapy against ischemic brain injury

Preconditioning induces ischemic tolerance by reprogramming the brain’s response to injury, reducing harmful inflammation and enhancing neuroprotective pathways. Seeking clinically applicable stimuli, we identified poly‑IC as a potent preconditioning agent that provides robust protection in vitro and in vivo across multiple murine ischemia‑reperfusion models, with minimal systemic inflammation. Poly‑ICLC activates interferon‑related genes shared with other preconditioning stimuli, and its protection requires IRF7 and type I interferon signaling. Using TLR9 knockout bone‑marrow chimeras, we found that CpG‑induced protection requires TLR9 expression on both hematopoietic and parenchymal cells. These findings highlight poly‑IC/poly‑ICLC as promising prophylactic therapies for ischemic injury.