Dl‐3‐N‐butylphthalide promotes angiogenesis and upregulates sonic hedgehog expression after cerebral ischemia in rats

INTRODUCTION: Dl‐3‐N‐butylphthalide (NBP), a small molecule drug used clinically in the acute phase of ischemic stroke, has been shown to improve functional recovery and promote angiogenesis and collateral vessel circulation after experimental cerebral ischemia. However, the underlying molecular mechanism is unknown. AIMS: To explore the potential molecular mechanism of angiogenesis induced by NBP after cerebral ischemia. RESULTS: NBP treatment attenuated body weight loss, reduced brain infarct volume, and improved neurobehavioral outcomes during focal ischemia compared to the control rats (P < 0.05). NBP increased the number of CD31(+) microvessels, the number of CD31(+)/BrdU(+) proliferating endothelial cells, and the functional vascular density (P < 0.05). Further study demonstrated that NBP also promoted the expression of vascular endothelial growth factor and angiopoietin‐1 (P < 0.05), which was accompanied by upregulated sonic hedgehog expression in astrocytes in vivo and in vitro. CONCLUSION: NBP treatment promoted the expression of vascular endothelial growth factor and angiopoietin‐1, induced angiogenesis, and improved neurobehavioral recovery. These effects were associated with increased sonic hedgehog expression after NBP treatment. Our results broadened the clinical application of NBP to include the later phase of ischemia.