Aspirin Exerts Neuroprotective Effects by Reversing Lipopolysaccharide-Induced Secondary Brain Injury and Inhibiting Matrix Metalloproteinase-3 Gene Expression

Objective. This study is aimed at exploring the possible neuroprotective mechanism of aspirin and the effect of bacterial endotoxin lipopolysaccharide (LPS) during cerebral ischaemia-reperfusion (CIRP) injury. Methods. We established three animal models: the CIRP, LPS, and CIRP+LPS models. Mortality...

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Autores principales: Depeng Feng, Dezhe Chen, Tuanzhi Chen, Xiaoqian Sun
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Publicado: Hindawi Limited 2021
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spelling oai:doaj.org-article:38ec836495884814a0b99d4e9f0db6f52021-11-22T01:11:18ZAspirin Exerts Neuroprotective Effects by Reversing Lipopolysaccharide-Induced Secondary Brain Injury and Inhibiting Matrix Metalloproteinase-3 Gene Expression1875-863010.1155/2021/3682034https://doaj.org/article/38ec836495884814a0b99d4e9f0db6f52021-01-01T00:00:00Zhttp://dx.doi.org/10.1155/2021/3682034https://doaj.org/toc/1875-8630Objective. This study is aimed at exploring the possible neuroprotective mechanism of aspirin and the effect of bacterial endotoxin lipopolysaccharide (LPS) during cerebral ischaemia-reperfusion (CIRP) injury. Methods. We established three animal models: the CIRP, LPS, and CIRP+LPS models. Mortality, the injured brain area, and the beam walking test were used to estimate the degree of cerebral injury among the rats. Immunohistochemistry and immunofluorescence were used to detect activated microglia, matrix metalloproteinase-3 (MMP-3), and osteopontin (OPN). Results. The injured brain area and mortality were dramatically reduced (p<0.01), and the beam walking test scores were elevated (p<0.01) in the acetylsalicylic acid (ASA) group compared to the control group. The number of microglia-, MMP-3-, and OPN-positive cells also increased. Furthermore, the number of GSI-B4, OPN, and MMP-3 cells decreased in the ASA group compared to the control group. After LPS stimulation, the number of microglia reached a peak at 24 h; at 7 d, these cells disappeared. In the ASA group, the number of microglia was significantly smaller (p<0.05), especially at 24 h (p<0.01), compared to the LPS group. Moreover, the injured brain area and the mortality were dramatically increased and the beam walking test scores were reduced (p<0.01) after LPS simulation following CIRP. The degree of injury in the ASA group resembled that in the control group. However, the number of MMP-3-immunoreactive neurons or microglia was significantly larger than that of the control group (p<0.05). In the ASA group, the MMP-3 expression was also considerably decreased (p<0.05). Conclusions. After CIRP, microglia were rapidly activated and the expression of MMP-3 and OPN significantly increased. For rats injected with LPS at reperfusion, the injured brain area and mortality also dramatically increased and the neurologic impairment worsened. However, ASA exhibited a neuroprotective effect during CIRP injury. Furthermore, ASA can reverse LPS-induced cerebral injury and inhibit the inflammatory reaction after CIRP injury.Depeng FengDezhe ChenTuanzhi ChenXiaoqian SunHindawi LimitedarticleMedicine (General)R5-920ENDisease Markers, Vol 2021 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Depeng Feng
Dezhe Chen
Tuanzhi Chen
Xiaoqian Sun
Aspirin Exerts Neuroprotective Effects by Reversing Lipopolysaccharide-Induced Secondary Brain Injury and Inhibiting Matrix Metalloproteinase-3 Gene Expression
description Objective. This study is aimed at exploring the possible neuroprotective mechanism of aspirin and the effect of bacterial endotoxin lipopolysaccharide (LPS) during cerebral ischaemia-reperfusion (CIRP) injury. Methods. We established three animal models: the CIRP, LPS, and CIRP+LPS models. Mortality, the injured brain area, and the beam walking test were used to estimate the degree of cerebral injury among the rats. Immunohistochemistry and immunofluorescence were used to detect activated microglia, matrix metalloproteinase-3 (MMP-3), and osteopontin (OPN). Results. The injured brain area and mortality were dramatically reduced (p<0.01), and the beam walking test scores were elevated (p<0.01) in the acetylsalicylic acid (ASA) group compared to the control group. The number of microglia-, MMP-3-, and OPN-positive cells also increased. Furthermore, the number of GSI-B4, OPN, and MMP-3 cells decreased in the ASA group compared to the control group. After LPS stimulation, the number of microglia reached a peak at 24 h; at 7 d, these cells disappeared. In the ASA group, the number of microglia was significantly smaller (p<0.05), especially at 24 h (p<0.01), compared to the LPS group. Moreover, the injured brain area and the mortality were dramatically increased and the beam walking test scores were reduced (p<0.01) after LPS simulation following CIRP. The degree of injury in the ASA group resembled that in the control group. However, the number of MMP-3-immunoreactive neurons or microglia was significantly larger than that of the control group (p<0.05). In the ASA group, the MMP-3 expression was also considerably decreased (p<0.05). Conclusions. After CIRP, microglia were rapidly activated and the expression of MMP-3 and OPN significantly increased. For rats injected with LPS at reperfusion, the injured brain area and mortality also dramatically increased and the neurologic impairment worsened. However, ASA exhibited a neuroprotective effect during CIRP injury. Furthermore, ASA can reverse LPS-induced cerebral injury and inhibit the inflammatory reaction after CIRP injury.
format article
author Depeng Feng
Dezhe Chen
Tuanzhi Chen
Xiaoqian Sun
author_facet Depeng Feng
Dezhe Chen
Tuanzhi Chen
Xiaoqian Sun
author_sort Depeng Feng
title Aspirin Exerts Neuroprotective Effects by Reversing Lipopolysaccharide-Induced Secondary Brain Injury and Inhibiting Matrix Metalloproteinase-3 Gene Expression
title_short Aspirin Exerts Neuroprotective Effects by Reversing Lipopolysaccharide-Induced Secondary Brain Injury and Inhibiting Matrix Metalloproteinase-3 Gene Expression
title_full Aspirin Exerts Neuroprotective Effects by Reversing Lipopolysaccharide-Induced Secondary Brain Injury and Inhibiting Matrix Metalloproteinase-3 Gene Expression
title_fullStr Aspirin Exerts Neuroprotective Effects by Reversing Lipopolysaccharide-Induced Secondary Brain Injury and Inhibiting Matrix Metalloproteinase-3 Gene Expression
title_full_unstemmed Aspirin Exerts Neuroprotective Effects by Reversing Lipopolysaccharide-Induced Secondary Brain Injury and Inhibiting Matrix Metalloproteinase-3 Gene Expression
title_sort aspirin exerts neuroprotective effects by reversing lipopolysaccharide-induced secondary brain injury and inhibiting matrix metalloproteinase-3 gene expression
publisher Hindawi Limited
publishDate 2021
url https://doaj.org/article/38ec836495884814a0b99d4e9f0db6f5
work_keys_str_mv AT depengfeng aspirinexertsneuroprotectiveeffectsbyreversinglipopolysaccharideinducedsecondarybraininjuryandinhibitingmatrixmetalloproteinase3geneexpression
AT dezhechen aspirinexertsneuroprotectiveeffectsbyreversinglipopolysaccharideinducedsecondarybraininjuryandinhibitingmatrixmetalloproteinase3geneexpression
AT tuanzhichen aspirinexertsneuroprotectiveeffectsbyreversinglipopolysaccharideinducedsecondarybraininjuryandinhibitingmatrixmetalloproteinase3geneexpression
AT xiaoqiansun aspirinexertsneuroprotectiveeffectsbyreversinglipopolysaccharideinducedsecondarybraininjuryandinhibitingmatrixmetalloproteinase3geneexpression
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