Simvastatin Reduces Neutrophils Infiltration Into Brain Parenchyma After Intracerebral Hemorrhage via Regulating Peripheral Neutrophils Apoptosis
Statins, known for their lipid-lowering effects, also have immunomodulatory properties. This study aims to examine whether systematic simvastatin administration could decrease polymorphonuclear neutrophils (PMNs) infiltration into brain tissue, as well as alleviate neuroinflammation in a rat model o...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-12-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fnins.2018.00977/full |
| _version_ | 1817969065583443968 |
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| author | Jianbo Zhang Xia Shi Na Hao Zhi Chen Linjie Wei Liang Tan Yujie Chen Hua Feng Qianwei Chen Qianwei Chen Gang Zhu |
| author_facet | Jianbo Zhang Xia Shi Na Hao Zhi Chen Linjie Wei Liang Tan Yujie Chen Hua Feng Qianwei Chen Qianwei Chen Gang Zhu |
| author_sort | Jianbo Zhang |
| collection | DOAJ |
| description | Statins, known for their lipid-lowering effects, also have immunomodulatory properties. This study aims to examine whether systematic simvastatin administration could decrease polymorphonuclear neutrophils (PMNs) infiltration into brain tissue, as well as alleviate neuroinflammation in a rat model of intracerebral hemorrhage (ICH). The ICH model was induced in adult male Sprague–Dawley rats by an injection of autologous blood. Animals randomly received simvastatin (i.p. 2 mg/kg) or vehicle daily from 5 days before ICH until sacrificed. Routine blood counts, brain water content, neurological scoring, immunofluorescence and RT-PCR were conducted to evaluate the anti-inflammatory effect of simvastatin following ICH. Furthermore, flow cytometric and western blotting analysis were implemented for elucidating the mechanisms involved in simvastatin-induced reduction of neutrophil brain-invading. Elevated PMNs count and neutrophil-to-lymphocyte ratio in circulation were detected in rat model of ICH, which was reversed by using simvastatin. Simvastatin effectively alleviated PMNs infiltration and proinflammatory factors release in perihematomal area, as well as attenuated ICH-induced brain edema and neurological deficits. Simvastatin significantly downregulated the expression of antiapoptotic protein-Mcl-1 while increased the level of proapoptotic protein-Bax and cleaved caspase 3 in PMNs. Simvastatin treatment significantly alleviated PMNs brain-infiltrating and subsequent neuroinflammatory reaction after ICH, in part by accelerating peripheral PMNs apoptosis through disorganized the expression of apoptotic related proteins. Our data provided new evidence for simvastatin application on patients with ICH. |
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| id | doaj.art-b88acb1a294b4c71ab461921c9d49fe0 |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-04-13T20:16:41Z |
| publishDate | 2018-12-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Neuroscience |
| spelling | doaj.art-b88acb1a294b4c71ab461921c9d49fe02022-12-22T02:31:41ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2018-12-011210.3389/fnins.2018.00977419802Simvastatin Reduces Neutrophils Infiltration Into Brain Parenchyma After Intracerebral Hemorrhage via Regulating Peripheral Neutrophils ApoptosisJianbo Zhang0Xia Shi1Na Hao2Zhi Chen3Linjie Wei4Liang Tan5Yujie Chen6Hua Feng7Qianwei Chen8Qianwei Chen9Gang Zhu10Department of Neurosurgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, ChinaDepartment of Nutrition, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, ChinaDepartment of Orthopedics, Chongqing Hospital of Traditional Chinese Medicine, Chongqing, ChinaDepartment of Neurosurgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, ChinaDepartment of Neurosurgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, ChinaDepartment of Neurosurgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, ChinaDepartment of Neurosurgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, ChinaDepartment of Neurosurgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, ChinaDepartment of Neurosurgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, ChinaDepartment of Neurosurgery, The 452 Hospital of Western Air Force, Chengdu, ChinaDepartment of Neurosurgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, ChinaStatins, known for their lipid-lowering effects, also have immunomodulatory properties. This study aims to examine whether systematic simvastatin administration could decrease polymorphonuclear neutrophils (PMNs) infiltration into brain tissue, as well as alleviate neuroinflammation in a rat model of intracerebral hemorrhage (ICH). The ICH model was induced in adult male Sprague–Dawley rats by an injection of autologous blood. Animals randomly received simvastatin (i.p. 2 mg/kg) or vehicle daily from 5 days before ICH until sacrificed. Routine blood counts, brain water content, neurological scoring, immunofluorescence and RT-PCR were conducted to evaluate the anti-inflammatory effect of simvastatin following ICH. Furthermore, flow cytometric and western blotting analysis were implemented for elucidating the mechanisms involved in simvastatin-induced reduction of neutrophil brain-invading. Elevated PMNs count and neutrophil-to-lymphocyte ratio in circulation were detected in rat model of ICH, which was reversed by using simvastatin. Simvastatin effectively alleviated PMNs infiltration and proinflammatory factors release in perihematomal area, as well as attenuated ICH-induced brain edema and neurological deficits. Simvastatin significantly downregulated the expression of antiapoptotic protein-Mcl-1 while increased the level of proapoptotic protein-Bax and cleaved caspase 3 in PMNs. Simvastatin treatment significantly alleviated PMNs brain-infiltrating and subsequent neuroinflammatory reaction after ICH, in part by accelerating peripheral PMNs apoptosis through disorganized the expression of apoptotic related proteins. Our data provided new evidence for simvastatin application on patients with ICH.https://www.frontiersin.org/article/10.3389/fnins.2018.00977/fullintracerebral hemorrhagestatinspolymorphonuclear neutrophilsapoptosisinflammation |
| spellingShingle | Jianbo Zhang Xia Shi Na Hao Zhi Chen Linjie Wei Liang Tan Yujie Chen Hua Feng Qianwei Chen Qianwei Chen Gang Zhu Simvastatin Reduces Neutrophils Infiltration Into Brain Parenchyma After Intracerebral Hemorrhage via Regulating Peripheral Neutrophils Apoptosis Frontiers in Neuroscience intracerebral hemorrhage statins polymorphonuclear neutrophils apoptosis inflammation |
| title | Simvastatin Reduces Neutrophils Infiltration Into Brain Parenchyma After Intracerebral Hemorrhage via Regulating Peripheral Neutrophils Apoptosis |
| title_full | Simvastatin Reduces Neutrophils Infiltration Into Brain Parenchyma After Intracerebral Hemorrhage via Regulating Peripheral Neutrophils Apoptosis |
| title_fullStr | Simvastatin Reduces Neutrophils Infiltration Into Brain Parenchyma After Intracerebral Hemorrhage via Regulating Peripheral Neutrophils Apoptosis |
| title_full_unstemmed | Simvastatin Reduces Neutrophils Infiltration Into Brain Parenchyma After Intracerebral Hemorrhage via Regulating Peripheral Neutrophils Apoptosis |
| title_short | Simvastatin Reduces Neutrophils Infiltration Into Brain Parenchyma After Intracerebral Hemorrhage via Regulating Peripheral Neutrophils Apoptosis |
| title_sort | simvastatin reduces neutrophils infiltration into brain parenchyma after intracerebral hemorrhage via regulating peripheral neutrophils apoptosis |
| topic | intracerebral hemorrhage statins polymorphonuclear neutrophils apoptosis inflammation |
| url | https://www.frontiersin.org/article/10.3389/fnins.2018.00977/full |
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