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The Wnt/β‐catenin coupled with HIF‐1α/ VEGF signal pathway involved neurovascular unit protection by galangin against permanent focal cerebral ischemia in rats (LB628)
Author(s) -
Li Shaojing
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.lb628
Subject(s) - galangin , medicine , ischemia , neuroprotection , neuroscience , pharmacology , pathology , chemistry , biology , biochemistry , kaempferol , antioxidant , quercetin
Background In recent years, the concept of the neurovascular unit (NVU) has emerged as a new paradigm for understanding the pathology of central nervous system (CNS) disease, including stroke. Our previous studies reported the neuroprotection of galangin on permanent focal cerebral ischemia in vivo, but its underlying mechanisms are far from clear. In this study, we investigated the effects of galangin on NVU functions and associated signal pathway in rats impaired by middle cerebral artery occlusion (MCAO)‐induced focal cerebral ischemia. Methods Neurological scores were used to reflect the therapeutic effect of galangin. Cerebral edema and the detection of Evan’s blue (EB) concentration in brain tissue were utilized to evaluate the permeability of BBB. The pathological changes of NVU ultrastructure and BBB permeability were observed by transmission electron microscopy (TEM) after MCAO visually. The protective mechanism of galangin was operated through Real‐time quantitative polymerase chain reaction (RT‐PCR) and Western blot. Results Results showed that galangin could ameliorate neurological scores and brain edema, reduce the concentration of EB in brain tissue after MCAO. Meanwhile, ultrastructural changes of NVU were improved by galangin. Moreover, the results of RT‐PCR and Western blot revealed that galangin protect NVU through Wnt/β‐catenin pathway coupled with HIF‐1α/vascular endothelial growth factor (VEGF). VEGF was activated in an HIF‐1α dependent way. VEGF and β‐catenin could be the key joints of these two coupled pathways. Conclusions All these data in this study firstly demonstrated that anti‐cerebral ischemia mechanism of galangin might through its regulation effect that enhance angiogenesis and neurogenesis in NVU. Galangin might function as a potential multi‐target drug in the treatment of ischemic stroke. Grant Funding Source : the National Natural Science Foundation of China (No. 81274133 and 81303261) and the Major Scientific and Technological Special Project for “Significant New Drugs Creation” (No. 2012ZX09103‐201‐055)