Dl-3-N-Butylphthalide Alleviates the Blood–Brain Barrier Permeability of Focal Cerebral Ischemia Reperfusion in Mice

Ischemic stroke occurs following arterial occlusion and subsequent blood flow cease, and restoration of blood supply by thrombolytic therapy may cause cerebral ischemic reperfusion (IR) injury resulting in breakdowns of blood–brain barrier (BBB). Dl-3-n-butylphthalide (NBP) is an extraction from Chinese celery Apium graveolens Linn seeds and has neuroprotective effects in ischemic stroke. This study explored effects of NBP on BBB disruption caused by cerebral IR and transformation of tight junctions (TJs)-associated proteins and caveolae. Our results demonstrated that NBP alleviated cerebral IR-induced deterioration of vascular permeability by up-regulating TJ-associated proteins but down-regulating caveolin-1. NBP significantly improved neurological function and cerebral blood flow but reduced cerebral edema and infarct volume after IR. In conclusion, NBP exerts neuroprotective effects through attenuating cerebral infarct volume and neurological deficit score, reducing cerebral edema and BBB permeability. The neuroprotective effect of NBP is possibly related to its ability to improve blood flow in cerebral ischemic areas. NBP may turn into a novel treatment drug to prevent BBB dysfunction in ischemic stroke. •Dl-3-n-butylphthalide significantly upregulates tight junctions-associated proteins.•Dl-3-n-butylphthalide significantly downregulates caveolin-1 expression.•Dl-3-n-butylphthalide significantly improves neurological function and cerebral blood flow.•Dl-3-n-butylphthalide significantly reduces cerebral edema and infarct volume after ischemic reperfusion.•Dl-3-n-butylphthalide alleviates reperfusion-induced deterioration of vascular permeability of blood brain barrier.