Simvastatin Reduces Neutrophils Infiltration Into Brain Parenchyma After Intracerebral Hemorrhage via Regulating Peripheral Neutrophils Apoptosis

Frontiers in Neuroscience

Zhi Chen¹  Liang Tan¹  Yujie Chen¹  Gang Zhu¹  Hua Feng¹  Jianbo Zhang¹  Linjie Wei¹  Qianwei Chen²  Xia Shi³  Na Hao⁴ 

[1] Department of Neurosurgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China;Department of Neurosurgery, The 452 Hospital of Western Air Force, Chengdu, China;Department of Nutrition, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China;Department of Orthopedics, Chongqing Hospital of Traditional Chinese Medicine, Chongqing, China;

关键词: intracerebral hemorrhage;    statins;    polymorphonuclear neutrophils;    apoptosis;    inflammation;   

DOI  :  10.3389/fnins.2018.00977

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown