Journal
BRAIN RESEARCH BULLETIN
Volume 168, Issue -, Pages 156-164Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.brainresbull.2020.12.023
Keywords
Angiopoietin-like 4; Acute ischemic stroke; Angiogenesis; Neurogenesis; Inflammation
Categories
Funding
- Fund of National Natural Science Foundation of China [NSFC 81271407]
- Incubating Program of Xuanwu Hospital of Capital Medical University [XWJL-2019015]
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In this study, we investigated the effects of ANGPTL4 on promoting angiogenesis and neurogenesis post-stroke in mice. The results showed that ANGPTL4 significantly reduced infarct volume, increased the number of BrdU(+), BrdU(+)/vWF(+) and BrdU(+)/DCX+ cells, and inhibited BrdU(+)/Iba1(+) cells. ANGPTL4 enhanced angiogenesis and neurogenesis post-stroke by upregulating AKT phosphorylation, reducing neuronal death, and inhibiting inflammatory response.
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 mu g/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 colabelling bromodeoxyuridine (BrdU) with von Willebrand factor (vWF), doublecortin (DCX), neuronal nuclei (NeuN) and Ibal 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 pen-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.
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