Angiopoietin-like 4 promotes angiogenesis and neurogenesis in a mouse model of acute ischemic stroke
| Autor: | Dayong Li, Suming Zhang, Jia Yang, Gang Deng, Zhandong Qiu |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Angiogenesis Neurogenesis Neovascularization Physiologic Subventricular zone Subgranular zone Angiopoietin 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine Angiopoietin-Like Protein 4 Animals Medicine cardiovascular diseases Cell Proliferation Ischemic Stroke Neovascularization Pathologic biology business.industry General Neuroscience Brain Doublecortin Mice Inbred C57BL Stroke Disease Models Animal 030104 developmental biology Endocrinology medicine.anatomical_structure chemistry biology.protein NeuN business Angiopoietins 030217 neurology & neurosurgery Bromodeoxyuridine |
| Zdroj: | Brain Research Bulletin. 168:156-164 |
| ISSN: | 0361-9230 |
| DOI: | 10.1016/j.brainresbull.2020.12.023 |
| Popis: | Objective The purpose of the present study is to investigate whether angiopoietin-like 4 (ANGPTL4) can promote angiogenesis and neurogenesis following stroke, as well as to explore the potential underlying mechanisms. Methods ANGPTL4 (40 μg/kg) or a vehicle was administered via tail vein beginning 5 min prior to electrocoagulation-induced stroke in male C57/B6 J mice. Infarct volume was measured via Nissl staining at day 3 post-stroke. Angiogenesis, neurogenesis and activation of microglia were evaluated by immunofluorescence co-labelling bromodeoxyuridine (BrdU) with von Willebrand factor (vWF), doublecortin (DCX), neuronal nuclei (NeuN) and Iba1 at day 7 post-stroke. The levels of p-AKT, T-AKT, VEGF, MPO, Fas and FasL in the ipsilesional brain were detected by Western blot analysis at day 1 post-stroke. Results Compared with the Vehicle group, ANGPTL4 reduced infarct volume significantly at day 3 post-stroke. ANGPTL4 significantly increased the number of BrdU+, BrdU+/vWF+and BrdU+/DCX+ cells in the peri-infarct zone, subventricular zone and subgranular zone and inhibited BrdU+/Iba1+ cells in the peri-infarct zone at day 7 post-stroke. The level of p-AKT and the ratio of phospho-AKT to total-AKT in the ipsilesional brain were significantly elevated, the levels of MPO, Fas and FasL were significantly declined; however, there was no significant difference at day 1 post-stroke between the VEGF and total-AKT levels in both groups. Conclusions ANGPTL4 enhances angiogenesis and neurogenesis post-stroke by upregulating the phosphorylation of AKT, reduces neuronal death and inhibits inflammatory response, which resultes from the inhibition of FasL/Fas expression and its downstream pathway. |
| Databáze: | OpenAIRE |
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