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Angiogenesis is a key physiological process that plays a key role in glioblastoma (GBM) progression and displays therapeutic resistance to antiangiogenic therapies. In this study, we aimed to identify whether vascular endothelial growth factor receptor 2(VEGFR2)monoclonal antibodies(mab)could inhibit tumorigenicity and the formation of vascular mimicry (VM) in GBM. The bioinformatic analysis from TCGA, CGGA, and TCPA databases and Immunohistochemistry (IHC) revealed that VEGFR2 is highly expressed in glioma tissues and results in a poor prognosis and is positively associated with VM markers (CD34 and PAS). The anti-VEGFR2 monoclonal antibodies(MSB0254)could inhibit the invasion, migration, and VM formation of U251 and primary glioma cells in vitro. In vivo, MSB0254 (m) could not only inhibit the growth of transplanted tumors of U251 and GL261 cells, but also significantly inhibit the expression of CD34, VEGFR2, Ki67, MMP2, MMP9 and reduce the expression of CD34/PAS and inhibit VM formation. The VEGFR2 monoclonal antibody could inhibit the angiogenesis and tumor growth of GBM by blocking the signaling pathway mediated by VEGFR2. It may become a new supplementary treatment for GBM.

To compare and analyze the efficacy and safety of traditional craniotomy and small bone window craniotomy in the treatment of hypertensive cerebral hemorrhage (HICH).Fifty-four patients with HICH treated with traditional craniotomy and small bone window craniotomy were retrospectively analyzed. The operation time, hospitalization time, preoperative, and postoperative CT analysis, Glasgow coma scale (GCS) score and Glasgow outcome scale (GOS) scores were analyzed.There were no significant differences in gender, age, hematoma volume, GCS score and pre-operative time between the 2 groups (P 0.05). The operation time and hospitalization time of the micro-bone window group were shorter than those of the traditional operation group (P 0.05). The GCS and GOS scores of the small bone window group after 3 days and 6 months were higher than those of the traditional operation group (P 0.05). However, there was no significant difference in hematoma clearance rate, re-bleeding rate and infection rate between the two groups (P 0.05).For patients with GCS 8-12 HICH, micro-bone window not only has the same effect as traditional bone window, but also has the advantages of shorter operation time and less trauma.

It was previously confirmed that the apoptotic and necrotic neurons are found during the acute post‐traumatic period, suggesting the induction of apoptosis after traumatic brain injury (TBI). To further explore the involvement of apoptotic factors in TBI, an apoptosis antibody array was conducted to measure the alterations of apoptotic factors in rat brain cortex after TBI. As a result, the Neurological Severity Scale (NSS) scores after TBI were increased, and the cell morphology of the brain cortex was destructed with increased neuronal apoptosis. Furthermore, the caspase‐3 activity was increased, and the apoptotic‐related factors TNF‐α and p53 were up‐regulated in the brain cortex. More importantly, in vitro experiments demonstrated that down‐regulation of TNF‐α in oxygen‐glucose deprivation/reoxygenation (OGD/R) cells increased cell viability and decreased apoptosis and the p53 expression. These results suggested the involvement of TNF‐α–induced apoptotic signalling pathway by activating p53 in the molecular mechanism of neurological injury.

Purpose 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

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.

Background Glioma is the most common malignancy in brain carcinoma with poor prognosis due to the lack of understanding of the mechanism underlying the disease. γ-interferon-inducible lysosomal thiol reductase (GILT) plays a critical role in the process of antigen processing. However, the role of GILT in the tumorigenesis of glioma remains unknown. Materials and methods The expression of GILT was analyzed by bioinformatics using the public database and by qPCR in three human glioma cell lines. Cell growth and viability were determined by Celigo and MTT assays, while cell cycle arrest and apoptosis were determined using flow cytometry. Giemsa staining was used to analyze the colony formation, while cell motility was assessed using transwell migration and invasion assays, as well as, using tumor growth in nude mice. Results GILT was highly expressed as observed in the public database on human gliomas and two human glioma cell lines, U373MG and U87MG cells. The downregulation of GILT by lentiviral-mediated silencing inhibits the cell growth, colony formation, and migration but promotes apoptosis and results in cell cycle arrest at the G0/G1 phase in the U373MG cells. Also, the knockdown of GILT inhibits tumor growth in vivo. Conclusion Elevated GILT is positively associated with glioma progression. GILT silencing suppresses cell proliferation, colony formation, migration, and tumor growth, and induces apoptosis and cell cycle arrest. GILT may serve as a potential target for the treatment of glioma.

Purpose 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

// Guangfu Di 1, 2, * , Hua Liu 1, 3, * , Xinhua Hu 1, * , Sansong Chen 2 , Zhichun Wang 2 and Hongyi Liu 1 1 Department of Neurosurgery, The Affiliated Brain Hospital, Nanjing Medical University, Nanjing, China 2 Department of Neurosurgery, Yijishan Hospital, Wannan Medical College, Wuhu City, China 3 Department of Neurosurgery, The First People’s Hospital of Kunshan, Jiangsu University, Suzhou, China * These authors have contributed equally to this work Correspondence to: Hongyi Liu, email: DGFYJSYY@163.com Keywords: intracranial injury, mild traumatic brain injury, infants Received: June 14, 2017 Accepted: August 28, 2017 Published: October 04, 2017 ABSTRACT Purpose : Mild traumatic brain injury (TBI) is common in children. The aim of this study was to identify clinical predictors of intracranial injuries on computed tomography (CT) in infants younger than 2 years old with mild TBI, which allow reducing number of imaging. Results : Of 214 enrolled infants with complete data, 30 (5.8%) sustained intracranial injuries. Younger age in months, severe injury mechanism and scalp hematomas were associated with traumatic intracranial injuries on CT. 71 had scalp hematomas and 143 had no scalp hematoma. Within infants with scalp hematomas, 26 sustained intracranial injuries and 45 presented normal. Intracranial injuries were significantly correlated with larger scalp hematomas and different scalp hematoma locations. Logistic regression analysis showed that scalp hematoma and mechanism of injury in infants younger than 2 years old with mild TBI was related to intracranial injuries (hazard ratio=38.291, P=0.0001; hazard ratio=0.174, P=0.001). In subgroup of mild TBI infants with scalp hematomas, logistic regression analysis showed age, scalp hematoma size and mechanism of injury were independently associated with intracranial injuries (hazard ratio=0.299, P=0.032; hazard ratio=5.272, P=0.006; hazard ratio=0.312, P=0.030). Methods : Between 2014 and 2016, we retrospectively enrolled infants

Background A skull fracture widely occurs in patients with traumatic brain injury, leading to intracranial hematoma, brain contusion, and intracranial infection. It also influences the prognosis and death of patients. This study aimed to discuss cases of patients with comminuted skull fractures. Methods From October 2015 to December 2018, 38 patients with comminuted skull fractures were admitted to the hospital. All patients underwent three-dimensional reconstruction of computed tomography scan images. Digital subtraction angiography or magnetic resonance venography was performed to find out the venous sinus. The clinical findings of the patients were significant regarding gender, age, injury mechanism, location, admission Glasgow Coma Scale (GCS), combined epidural, subdural, cerebral contusion, intracranial pneumatosis, maximum depth of depression, admission to surgery, dural tear, post-operative cerebrospinal fluid leakage, post-operative infection, and Glasgow Outcome Scale (GOS) 3 months after surgery. Results The incidence of traffic accidents, fall from a height, railway accidents, fall of an object, and chop injury was 60.5%, 18.4%, 13.2%, 5.3%, and 2.6%, respectively. Intra-operative dural trar negatively correlated with epidural hematoma, cerebral contusion, and subdural hematoma. Also, post-operative infection negatively correlated with intracranial pneumatosis, depth of fracture depression, and pre-operative cerebrospinal fluid leakage. No correlation was found between contusion, subdural hematoma, intracranial pneumatosis, depth of fracture depression, and post-operative infection. The GOS score positively correlated with age, pre-operative cerebrospinal fluid leakage, and admission GCS score. Conclusions A perfect pre-operative examination is a key to successful surgery. Further studies should be conducted to find out more effective treatments for traumatic comminuted skull fractures.

Background Glioma is the most common primary malignant tumor with poor prognosis due to the lack of understanding the mechanism underlying the disease and the early diagnosis indexs. It is necessary to identify molecular signatures for predicting the overall prognosis of glioma. Adipocyte enhancer binding protein1 (AEBP1) acts as a transcriptional repressor and plays a role in adipogenesis and smooth muscle cell differentiation. However, its role in glioma remains unclear. Materials and methods AEBP1 expression was analyzed by bioinformatics using the public database and by qPCR and western blotting in human glioma tissues. AEBP1 downregulation was performed by lipofectamine3000-mediated siRNA transfection. Cell proliferation and invasion were determined by cell counting kit-8 and transwell assays, while early cell apoptosis was determined by flow cytometry. The proteins of downstream NF-κB signaling pathway were determined by western blotting. Results AEBP1 is highly expressed in human gliomas. Lipofectamine 3000-mediated siRNA transfection stably and efficiently suppressed AEBP1 mRNA and protein expression in human glioma cells. AEBP1 downregulation inhibited cell proliferation and invasion, but promoted early cell apoptosis. Also, AEBP1 knockdown in glioma cells decreased the expression of NF-κB1. Furthermore, the downstream of NF-κB signaling pathway, Bax, caspase-3 are increased, while MMP2 and Bcl-2 are decreased in glioma cells. Conclusion Elevated AEBP1 is positively associated with poor prognosis of glioma. AEBP1 downregulation suppressed cell proliferation and invasion, but promoted early cell apoptosis. AEBP1 downregulation suppressed the cell proliferation and invasion may by inhibiting the NF-κB signaling pathway.

Acute lung injury (ALI) is one of the severe complications in patients with traumatic brain injury (TBI), contributing to the high mortality. Ghrelin has protective effects against various inflammatory diseases, but the effects of Ghrelin on TBI-induced ALI and its mechanisms remain unknown. In this study, Ghrelin administration was performed on the mice with TBI, then histological change in cortex and lung tissues, lung vascular permeability and macrophage number in bronchoalveolar lavage fluid (BALF) were examined, respectively. Simultaneously, the alterations of proinflammatory factors and pyroptosis-related proteins in lung tissues were detected. As a result, TBI-induced ALI was ameliorated after Ghrelin treatment, which was demonstrated by improved histology, reduced lung vascular permeability, and peripheral macrophage number. Furthermore, Ghrelin decreased the mRNA levels of proinflammatory factors (IL-1β, IL-6, TNF-α and IL-18), the protein levels of pyroptosis-related proteins (NLRP3, Caspase1-P20, HMGB1 and Gasdermin D), and the phosphorylation levels of NF-κB in lung tissues. These results showed that Ghrelin attenuating TBI-induced ALI might be via ameliorating inflammasome-induced pyroptosis by blocking NF-κB signal, which are important for the prevention and treatment of TBI-induced ALI.

Traumatic brain injury (TBI) is a primary cause of disability and mortality. Ghrelin, a gastrointestinal hormone, has been found to have protective effects for the brain, but the molecular mechanism of these neuroprotective effects of ghrelin remains unclear. In this study, an electronic cortical contusion impactor was used to establish a rat TBI model and we investigated the effect of ghrelin on brain repair by neurological severity score and histological examination. An antibody array was employed to uncover the molecular mechanism of ghrelin’s neuroprotective effects by determining the alterations of multiple proteins in the brain cortex. As a result, ghrelin attenuated brain injury and promoted brain functional recovery. After TBI, 13 proteins were up-regulated in the brain cortex, while basic fibroblast growth factor (bFGF) and fibroblast growth factor-binding protein (FGF-BP) were down-regulated after ghrelin treatment. It is known that bFGF can induce angiogenesis in the brain and accelerate wound healing, which can be further enhanced by FGF-BP. Based on the previous studies, it is hypothesized that the exogenous ghrelin curing TBI might cause the closure of bFGF and FGF-BP functions on wound healing, or ghrelin might exert the neuroprotective effects by competitively inhibiting bFGF/FGF-BP-induced neovascularization. Whether the combinational administration of ghrelin and bFGF/FGF-BP can enhance or weaken the therapeutic effect on TBI requires further research.

Glioma is the most common adult malignant primary brain tumor; however, the effect of chemotherapy is often limited by drug-resistance and poor prognosis is common. Ring finger protein 138 (RNF138) belongs to the E3 ligase family, and has significantly higher expression level in glioma tissue than in noncancerous brain tissues. Epithelial-mesenchymal-transition (EMT) has a critical role in cancer invasion and metastasis, ultimately leading to increased cell motility and resistance to genotoxic agents. Extracellular-signal regulated kinase (Erk) pathways promote the growth of glioma cells and enhance tumor invasion, with a role in the progression of EMT. However, the association between RNF138 and human glioma progression remains poorly understood. Relatively little is known about the association between RNF138, Erk, and EMT in glioma progression. In the current study, experiments were performed to explore the potential roles and mechanisms of RNF138 in glioblastoma in vitro and in vivo. Glioma cell line proliferation, migration and invasion were inhibited by knockdown of RNF138 in vitro. By lowering the RNF138 expression, cleaved caspase3 and E-cadherin were upregulated, while phospho-Erk1/2, vimentin, MMP2, HIF-1α and VEGF were downregulated in U87 and U251 cells in vitro. In vivo findings revealed that the growth of U87 cell-transplanted tumors in nude mice was inhibited in tumors with RNF138 knockdown. These findings suggested that downregulation of RNF138 inhibited glioma cell proliferation, migration, and invasion, and reversed EMT, potentially via Erk signaling pathway. Therefore, RNF138 may be a potential therapeutic target against glioma.

Objective Traumatic brain injury (TBI) occurs commonly in children. Repeat computed tomography (CT) follow up of TBI patients is often scheduled to identify progressive hemorrhagic injury (PHI). However, the utility of repeated CT scans, especially in children with mild TBI [Glasgow Coma Scale (GCS) scores of 13–15], has been debated. The purposes of the present study were to identify clinical predictors of PHI in children with mild TBI and to clarify relevant clinical factors via radiological examination. Methods From 2014 to 2016, we retrospectively enrolled children