ABSTRACT Aims Dl‐3‐n‐butylphthalide (NBP) is a novel agent for acute ischemic stroke. This study aimed to investigate its effects on cortical angiogenesis and vasodilation during stroke recovery. Methods Mice underwent distal middle cerebral artery occlusion (dMCAO) and subsequently received NBP treatment. Therapeutic efficacy was measured by neurological deficits and infarct size. Angiogenesis was assessed by immunofluorescent staining. Laser speckle and two‐photon microscopy imaging were employed to evaluate dynamic changes in cortical cerebral blood flow and vascular structure in vivo. The modulation of the Akt/GSK‐3β signaling pathway was detected by western blotting. Results NBP administration promoted neurological recovery and reduced infarct size in the subacute phase. It facilitated cerebral blood flow and vasodilation, enhanced angiogenesis as evidenced by increased BrdU + /CD31 + cells and improved astrocyte/pericyte coverage around microvessels. Moreover, the pro‐angiogenesis effect of NBP depends on the activation of the Akt/GSK‐3β pathway, and this effect is blocked by LY294002. Conclusion In conclusion, NBP enhances recovery after ischemic stroke by promoting cortical angiogenesis and vasodilation through activation of the Akt/GSK‐3β pathway. These findings highlight its therapeutic potential for delayed intervention in ischemic stroke.
Zhang et al. (Mon,) studied this question.