2. Academic Validation
  3. Dl-3-n-Butylphthalide Promotes Cortical Angiogenesis via Akt/GSK-3β Signaling in Ischemic Stroke Mice

Dl-3-n-Butylphthalide Promotes Cortical Angiogenesis via Akt/GSK-3β Signaling in Ischemic Stroke Mice

  • CNS Neurosci Ther. 2025 Dec;31(12):e70698. doi: 10.1002/cns.70698.
Lan Zhang 1 2 3,  Shanshan Wei 4,  Jian Zhang 2 3 5,  Rong Chen 2 3,  Jiangyong Miao 1 2 3,  Lina Wang 1 2 3,  Peipei Zhang 1 2 3,  Wenyan Shang 1 2 3,  Renhao Xu 2 3,  Xiangjian Zhang 1 2 3,  Cong Zhang 1 2 3
Affiliations

Affiliations

  • 1 Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China.
  • 2 Hebei Key Laboratory of Vascular Homeostasis and Hebei Collaborative Innovation Center for Cardio-Cerebrovascular Disease, Shijiazhuang, Hebei, People's Republic of China.
  • 3 The Key Laboratory of Clinical Neurology, Ministry of Education, Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China.
  • 4 Department of Neuromuscular Disease, The Third Affiliated Hospital of Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China.
  • 5 Department of Geriatrics, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China.
PMID: 41373119 DOI: 10.1002/cns.70698
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.

Keywords

Akt/GSK‐3β pathway; angiogenesis; dl‐3‐n‐butylphthalide; ischemic stroke; vasodilation.

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