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

Abstract

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.

TGF‐β1 and IL‐17A comediate the protumor phenotype of neutrophils to regulate the epithelial‐mesenchymal transition in oral squamous cell carcinoma

“…We first used immunofluorescence staining to determine whether neutrophils infiltrate into OSCC tissue, Myeloperoxidase (MPO) and CD66b served as markers of human neutrophils 4,22 . MPO + CD66b + neutrophils were increased in OSCC tissue (n = 5) compared with normal mucosa (n = 5; Figure 1A).…”

Lipophilic vs. hydrophilic statins and psychiatric hospitalizations and emergency room visits in US Veterans with schizophrenia and bipolar disorder

“…The neutrophil:lymphocyte ratio (NLR) has been reported to be elevated in acute relapse inschizophrenia [ 168 ] and bipolar disorder [ 169 ],in particular in functionally relevant cognitive dysfunction and functional deterioration, as well as in increased suicide risk in euthymic bipolar individuals [ 170 ]. In tight experimental conditions, pretreatment with statins has been shown to prevent elevated NLR [ 171 ] after experimental stroke in rodents.…”

Effects of homocysteine-induced endoplasmic reticulum protein on endoplasmic reticulum stress, autophagy, and neuronal apoptosis following intracerebral hemorrhage

“…ICH models in vivo and in vitro are established to simulate clinical ICH. In vivo, the mice model of ICH was built by a nigrostriatal injection of autologous blood which is carried out easily to mimic human ICH ( Zhang et al, 2018 ). In vitro, we use hemin to treat primary cortical neurons, which can also mimic human ICH.…”