The Neuroprotective Effect of l-Borneolum on Cerebral Ischemic Stroke by Regulating Dll4/Notch1 Pathway

Abstract Aiml-Borneolum is a monoterpene compound witch deserved from Blumea balsamifera (L.) DC, this study aimed to investigate the potential mechanism of l-borneolum on cerebral ischemic stroke (CIS) rats and provide evidence for the development of l-borneolum in CIS.MethodsPermanent middle cerebral artery occlusion (pMCAO) model rats were applied to this study. Neurological function was assessed by modified neurological severity scores (mNSS) and Longa neurological function scoring methods. The pathological changes of cerebral tissue were evaluated by 2,3,5-triphenyltetrazolium chloride (TTC) and hematoxylin-eosin (HE) staining. Ultrastructure of blood brain barrier (BBB) was observed by transmission electron microscopy. Additionally, the expression of Notch1, Dll4, Hey1, Hes1, Hes5, VEGFA and p65 in the cortex were determined by Western blotting (WB) while expression of caspase 3 were determined by immunohistochemical method (IHC). Resultsl-Borneolum improved neurological function in a dose-dependently. l-Borneolum significantly alleviated brainstem edema and inflammation, as well as improved the ultrastructure of capillary and BBB in cortex. Moreover, 0.2 g/kg l-borneolum substantially decreased the protein expressions of Dll4, Notch1, Hes1, Hes5, and VEGFA in the cortex while decreased the level of Caspase-3 in the cortex of rats. Conclusionsl-Borneolum could repair neurological function by regulating Dll4/Notch1 signaling pathway.