IntroductionS100 calcium-binding protein A8 (S100A8) is also known as macrophage-related protein 8, which is involved in various pathological processes in the central nervous system post-traumatic brain injury (TBI), and plays a critical role in inducing inflammatory cytokines. Accumulating evidences have indicated that toll-like receptor 4 (TLR4) is considered to be involved in inflammatory responses post TBI. The present study was designed to analyze the hypothesis that S100A8 is the key molecule that induces inflammation via TLR4 in TBI.MethodsThe weight-drop TBI model was used and randomly implemented on mice that were categorized into six groups: Sham, NS, S100A8, S100A8+TAK-242, TBI, and TBI+TAK-242 groups. In the S100A8+TAK-242 and TBI+TAK-242 groups, at half an hour prior to the intracerebroventricular administration of S100A8 or TBI, mice were intraperitoneally treated with TAK-242 that acts as a selective antagonist and inhibitor of TLR4. Furthermore, the protein recombinant of S100A8 was injected into the lateral ventricle of the brain of mice in the S100A8 and S100A8+TAK-242 groups. Sterile normal saline was injected into the lateral ventricle in the NS group. To evaluate the association between S100A8 and TLR4, Western blot, immunofluorescence, enzyme-linked immunosorbent assay (ELISA), and Nissl staining were employed. Simultaneously, the neurological score and brain water content were assessed. In the in vitro analysis, BV-2 microglial cells were stimulated with lipopolysaccharide LPS or S100A8 recombinant protein, with or without TAK-242. The expression of the related proteins was subsequently detected by Western blot or enzyme-linked immunosorbent assay.ResultsThe levels of S100A8 protein and pro-inflammatory cytokines were significantly elevated after TBI. There was a reduction in the neurological scores of non-TBI animals with remarkable severe brain edema after the intracerebroventricular administration of S100A8. Furthermore, the TLR4, p-p65, and myeloid differentiation factor 88 (MyD88) levels were elevated after the administration of S100A8 or TBI, which could be restored by TAK-242. Meanwhile, in the in vitro analysis, due to the stimulation of S100A8 or LPS, there was an upregulation of p-p65 and MyD88, which could also be suppressed by TAK-242.ConclusionThe present study demonstrated that the TLR4-MyD88 pathway was activated by S100A8, which is essential for the development of inflammation in the brain after TBI.

Background: S100A8 is involved in the pathological processes of a variety of central nervous system(CNS) diseases related to inflammation including traumatic brain injury (TBI). However, the underlying mechanism for the induction of inflammation in the brain by S100A8 after TBI remains unclear, which was investigated in the present study.Methods: The weight-drop TBI model was used in this study. The mice were randomly assigned into 5 groups: the Sham, S100A8, S100A8 + TAK-242, TBI, and TBI + TAK-242 groups. In the S100A8 + TAK-242 and TBI + TAK-242 groups, mice were treated with TAK-242, an inhibitor of Toll-like receptor (TLR) 4, intraperitoneally at half an hour before TBI. In the S100A8 and S100A8 + TAK-242 groups, S100A8 recombinant protein was injected into the lateral ventricle of the brain. To explore the relationship between S100A8 and TLR4, Western Blot (WB), immunofluorescence, enzyme-linked immunosorbent assay (ELISA) and Nissl staining were employed. Neurological score and the brain water content were also assessed. Additionally, BV-2 microglial cells were stimulated with lipopolysaccharide (LPS) or S100A8 recombinant protein with/without TAK-242 in vitro. The expressions of the related proteins were subsequently detected with WB or ELISA.Results: The levels of S100A8 protein and pro-inflammatory cytokines were significantly increased after TBI. After intracerebroventricular administration of S100A8, the neurological scores of non-TBI animals were decreased remarkably with severe brain edema. Furthermore, the levels of TLR4, p-p65 and myeloid differentiation factor 88(MyD88) were all increased after S100A8 administration or TBI, which could be restored by TAK-242. Meanwhile, p-p65 and MyD88 were upregulated after S100A8 or LPS stimulation in vitro, which also could be suppressed by TAK-242.Conclusions: The present study demonstrated that TLR4-MyD88 pathway was activated by S100A8, which was essential to the development of inflammation in the brain after TBI.

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Traumatic brain injury (TBI) is a major cause of death and disability worldwide. A sequence of pathological processes occurred when there is TBI. Previous studies showed that sphingosine-1-phosphate receptor 1 (S1PR1) played a critical role in inflammatory response in the brain after TBI. Thus, the present study was designed to evaluate the effects of the S1PR1 modulator FTY720 on neurovascular unit (NVU) after experimental TBI in mice. The weight-drop TBI method was used to induce TBI. Western blot (WB) was performed to determine the levels of SIPR1, claudin-5 and occludin at different time points. FTY720 was intraperitoneally administered to mice after TBI was induced. The terminal deoxynucleotidyl transferase-dUTP nick end labeling (TUNEL) assay was used to assess endothelial cell apoptosis. Immunofluorescence and WB were performed to measure the expression of tight junction proteins: claudin-5 and occludin. Evans blue (EB) permeability assay and brain water content were applied to evaluate the blood-brain barrier (BBB) permeability and brain edema. Immunohistochemistry was performed to assess the activation of astrocytes and microglia. The results showed that FTY720 administration reduced endothelial cell apoptosis and improved BBB permeability. FTY720 also attenuated astrocytes and microglia activation. Furthermore, treatment with FTY720 not only improved neurological function, but also increased the survival rate of mice significantly. These findings suggest that FTY720 administration restored the structure of the NVU after experimental TBI by decreasing endothelial cell apoptosis and attenuating the activation of astrocytes. Moreover, FTY720 might reduce inflammation in the brain by reducing the activation of microglia in TBI mice.

To explore the risk factors of the evolution of traumatic subdural effusion (TSE) into chronic subdural hematoma (CSDH). Materials and Methods: The 70 patients' gender, age, location of effusion, unilateral and bilateral, Glasgow coma score (GCS) at admission, presence or absence of brain contusion, the time of effusion appeared, daily amount of mannitol, mannitol number of days used, with or without atorvastatin calcium tablets, with or without antiplatelet aggregation drugs, with or without anticoagulant drugs, with or without abnormalities in blood coagulation routines, computed tomography (CT) layer height, the thickness, and CT value of the first effusion were analyzed by single factor. Logistic multivariate regression analysis was performed on the statistically significant indicators. Power of the regression model was evaluated using receiver operating characteristic (ROC) curve. Results: Univariate analysis showed that the presence or absence of brain contusion, the time of effusion appeared, atorvastatin calcium tablets use or not, the CT value of the effusion, and TSE into CSDH evolution varied significantly compared to the non-evolved group (P<0.05). Logistic multivariate regression analysis showed that combined brain contusion (odds ratio (OR)=16.247, 95% confidence interval (CI), 1.831-144.157, P = 0.012), early onset of effusion (OR = 0.573, 95% CI: 0.349-0.941, P = 0.028), atorvastatin calcium tablets not used after effusion (OR = 60.028, 95% CI: 6.103-590.399, P = 0.0001), and high CT value (OR = 1.285, 95% CI: 1.067-1.547, P = 0.008) were risk factors for the evolution of TSE into CSDH. The ROC model suggested that the prediction of these risk factors had high diagnostic accuracy. Conclusion: TSE patients with brain contusion, early onset of effusion, without the usage of atorvastatin calcium tablets after effusion, and high CT value of the first effusion are at a risk of evolving into CSDH.

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BackgroundFOSB is reported to be an oncogene in a variety of tumors. However, the expression and role of FOSB in glioma remain obscure. In this study, we aimed to explore the expression of FOSB in glioma and its biological role in glioblastoma multiforme (GBM).MethodsWestern blot, immunohistochemical staining, and quantitative real-time polymerase chain reaction (RT-qPCR) were used to detect the expression of FOSB in clinical samples. FOSB was knocked down in cells to determine the effects of FOSB on the phenotypic changes of tumors by plate cloning, CCK-8 assay, and Transwell assay. Finally, subcutaneous tumorigenesis in nude mice was used to observe the tumorigenesis of glioma cell lines after the knockdown of the FOSB gene.ResultsFOSB expression was higher in glioma compared with normal brain tissue. After the downregulation of FOSB, the expression of cleaved caspase-3 increased. Plate cloning and CCK-8 experiments showed that the proliferation of glioma cell lines decreased. The Transwell assay demonstrated that the glioblastoma cell lines had lower migration ability after the knockdown of FOSB. Finally, the tumor volume of U87 glioma cells in group sh-FOSB was smaller than that in the control group. The TUNEL staining in vitro showed that the apoptosis of sh-FOSB glioma cells increased.ConclusionFOSB was highly expressed in glioma tissues. The viability of glioma cells decreased, and the ability of glioma cells to proliferate and migrate was reduced when FOSB was downregulated. Hence, FOSB may promote the development and migration of gliomas.

Objective This study aims to reduce the tissue damage during craniotomy with retrosigmoid approach. A modified sickle-shaped skin incision was developed, and a new burr-hole positioning method was proposed. Methods Five adult cadaveric heads (10 sides) were used in this study. The sickle-shaped skin incision was performed during craniotomy. The nerves, blood vessels, and muscles were observed and measured under a microscope. Additionally, 62 dry adult skull specimens (left sided, n = 35; right sided, n = 27) were used to measure the distance between the most commonly used locating point (asterion [Ast] point) and the posteroinferior point of the transverse sigmoid sinus junction (PSTS) (Ast-PSTS), as well as the distance between the new locating O point and the PSTS (O-PSTS). Then, the reliability of the new locating O point was validated on the same five adult cadaveric heads (10 sides) used for the sickle-shaped skin incision. Results The sickle-shaped skin incision reduced the damage to the occipital nerves, blood vessels, and muscles during the surgery via a retrosigmoid approach. The dispersion and variability of O-PSTS were smaller than those of Ast-PSTS. Conclusion The sickle-shaped skin incision of the retrosigmoid approach can reduce the tissue damage and can completely expose the structures in the cerebellopontine angle. The modified O point is a more reliable locating point for a burr-hole surgery than the Ast point.