Computed tomographic angiography to analyze dangerous vertebral artery anomalies at the craniovertebral junction in patients with basilar invagination.

OBJECTIVE: Failure to detect dangerous anatomic vertebral artery anomalies (AVAAs) and dangerous functional vertebral artery anomalies (FVAAs) at the craniovertebral junction (CVJ) in patients with basilar invagination (BI) can result in major complications such as intraoperative vertebral artery injury, brain infarctions, and even death. Iatrogenic vertebral artery injury is a rare but severe complication of cervical spine surgery. We aimed to evaluate dangerous vertebral artery anomalies at the CVJ in patients with BI using computed tomographic angiography (CTA). METHODS: CTA images of 61 BI patients were retrospectively analyzed to evaluate AVAAs and FVAAs at the CVJ. Dangerous AVAAs include a persistent first intersegmental artery (FIA), fenestration of the vertebral artery (FEN), and posterior inferior cerebellar artery with an extradural C1/2 origin (PICA-C1/2). Dangerous FVAAs include a dominant vertebral artery (DVA) and hypoplastic vertebral artery ending in the PICA (HVA-PICA) without joining the basilar artery. RESULTS: Overall, 31 female and 30 male patients (mean age, 42.3 years) were included. The incidences of FIA, FEN, and PICA-C1/2 were 29.5 % (18/61), 3.3 % (2/61), and 3.3 % (2/61), respectively, whereas the incidences of DVA and HVA-PICA were 36.1 % (22/61) and 1.65 % (1/61), respectively. CONCLUSION: Dangerous vertebral artery anomalies at the CVJ have a high incidence in patients with BI. Preoperative CTA is highly recommended in such patients to identify anomalous vertebral arteries and reduce the risk of intraoperative injury.

Hypertonic saline improves brain edema resulting from traumatic brain injury by suppressing the NF-κB/IL-1ß signaling pathway and AQP4.

Although hypertonic saline (HS) has been extensively applied to treat brain edema in the clinic, the precise mechanism underlying its function remains poorly understood. Therefore, the aim of the present study was to investigate the therapeutic mechanism of HS in brain edema in terms of aquaporins and inflammatory factors. In the present study, traumatic brain injury (TBI) was established in male adult Sprague-Dawley rats, which were continuously administered 10% HS by intravenous injection for 2 days. In addition, brain edema and brain water content were detected by MRI and wet/dry ratio analysis and histological examination, respectively. Immunohistochemical staining for albumin and western blotting for occludin, zonula occludens-1 and claudin-5 was performed to evaluate the integrity of the blood-brain barrier. Aquaporin 4 (AQP4) expression was also analyzed using western blotting and reverse transcription-quantitative PCR, whilst interleukin (IL)-1ß and NF-κB levels were measured using ELISA. It was demonstrated that HS treatment significantly reduced brain edema in TBI rats and downregulated AQP4 expression in cerebral cortical tissues around the contusion site. In addition, IL-1ß and NF-κB levels were found to be downregulated after 10% HS treatment. Therefore, results from the present study suggested that HS may protect against brain edema induced by TBI by modulating the expression levels of AQP4, NF-κB and IL-1ß.

TRIM28 is overexpressed in glioma and associated with tumor progression.

BACKGROUND: Tripartite motif containing 28 (TRIM28) is a transcriptional co-factor targeting many genes with pleiotropic biological activities, but the study on the role of TRIM28 in glioma is rare. METHODS: To explore the function of TRIM28 in glioma, we first detected the expression levels of TRIM28 in glioma tissues and analyzed the correlations of TRIM28 expression with clinicopathological variables of patients in 85 cases of glioma. Meanwhile, we used shRNA to knockdown TRIM28 in glioma cell lines to detect the biological functions of TRIM28 in cell and animal experiments. RESULTS: We found that TRIM28 was expressed at significantly higher level in glioma tissues than in non-tumor brain, and TRIM28 expression correlated significantly with tumor malignancy. Furthermore, TRIM28 higher expression was also correlated with poor survival of glioma patients (P<0.01). Functionally, knockdown of TRIM28 could significantly inhibit cell proliferation and migration in glioma cells. Additionally, we found that TRIM28 could inhibit the expression of E-cadherin significantly by reducing its mRNA stability at the post-transcriptional level. CONCLUSION: Our results suggest that TRIM28 overexpression is correlated with glioma malignant progression and patients' poor survival, so targeting TRIM28 could be an efficacious strategy in glioma.

Ketohexokinase is involved in fructose utilization and promotes tumor progression in glioma.

Many studies have pinpointed that fructose could be utilized as a carbon source in some cancers, and we also defined that glioma cells could utilize fructose to maintain themselves survival and proliferation depending on GLUT5 expression recently. However, ketohexokinase (KHK), as a key enzyme involved in fructose catabolism, drew less attention in cancers, especially in glioma. In the present study, we first analyzed the expression levels of KHK in glioma tissues and the correlations of KHK expression with clinicopathological variables of patients with glioma. Meanwhile, we detected the effect of silencing KHK on the biological functions of glioma cells in fructose medium. From the results, we found that KHK was expressed at significantly higher level in glioma tissues than in non-tumor brain, and KHK expression was significantly correlated with tumor malignancy and poor survival of glioma patients (p < 0.01). Functionally, knockdown of KHK could significantly inhibit cell proliferation and migration of glioma cells in fructose medium. Furthermore, we investigated the KHK expression level after long-time treatment with fructose, and detected the change of cell biological behaviour, then we found that the expression level of KHK was significantly increased and these cells showed more malignant properties. Taken together, our results suggest that high fructose diet and KHK overexpression are correlated with glioma malignant progression and patients' poor survival, and we believe this hypothesis would open the door for novel therapeutic agents and mentalities for glioma.

GLUT5 increases fructose utilization and promotes tumor progression in glioma.

Fructose is now such an important component of human diets, and several studies have found that some cancer cells could utilize fructose to overcome low glucose micro-environment, but the study on the role of fructose in glioma is rare. To explore the role of fructose in glioma, we detected the proliferation and colony formation ability of glioma cells in fructose medium, and found that the abilities of proliferation and colony formation of glioma cells in fructose medium were similar with abilities in glucose medium, however, fructose just partly restored proliferation ability of normal glial cells. To explore the mechanism, we compared the expression level of GLUT5 (Glucose transporter type 5) in these cell lines, and the results showed that glioma cell lines had higher GLUT5 expression than normal glial cell lines. And knockdown of GLUT5 could significantly inhabit cell proliferation of glioma cells in fructose medium. Furthermore, we found that GLUT5 was also higher expressed in glioma tissues, and GLUT5 expression correlated significantly with glioma malignancy and poor survival of glioma patients (p < 0.01). In addition, we also demonstrated that knockdown of GLUT5 could significantly inhabit tumor proliferation in vivo, and intake fructose could increase tumor volume prominently. Taken together, our data show that fructose can be used by glioma cells, and restrict the fructose intake or targeting GLUT5 could be efficacious strategies in glioma.

Tirofiban combined with urokinase selective intra-arterial thrombolysis for the treatment of middle cerebral artery occlusion.

The aims of the present study were to establish a model of embolic stroke in rabbits and to evaluate the efficacy and safety of intra-arterially administered tirofiban combined with urokinase thrombolysis. The middle cerebral artery occlusion model (MCAO) of embolic stroke was established in New Zealand rabbits via an autologous clot. The model rabbits were allocated at random into four groups: Tirofiban group (T group), urokinase group (UK group), tirofiban and urokinase group (T + UK group) and the control group (C group). The recanalization rate, relative-apparent diffusion coefficient (rADC) and neurological function deficit score (NFDS) values were compared among the four groups. The recanalization rate, rADC and NFDS values were improved in the T + UK group compared with the other groups. In summary, the intra-arterial administration of tirofiban combined with urokinase thrombolysis was a more effective intervention in an MCAO model compared with intra-arterial urokinase alone, and may promote reperfusion and reduce infarct volume.

Feasibility and limitations of C1 lateral mass screw placement in patients of atlas assimilation.

BACKGROUND: C1 lateral mass is a common place for screw fixation in normal anatomy; whereas there is no research about whether screw placement is suitable in patients of C1 assimilation (C1A). OBJECTIVE: To study the feasibility and limitations of C1 lateral mass screw placement in patients with C1A. PATIENTS AND METHODS: From April 2008 to March 2009, C1 lateral mass of 17 C1A patients with atlantoaxial instability (AAI) or dislocation (AAD) was observed and measured using CT reconstruction; and factors determining C1 lateral mass screw placement were studied before and during the operation. RESULTS: A screw of 3.5mm in diameter could be virtually inserted in 31 C1 lateral masses of total 17 C1A patients with maximal length of the screw 18.1±2.7mm; but the entry point of screw had to be modified in the posterior part of inferior facet of C1 instead of posterior middle wall of C1 lateral mass. Clinically, abnormal course of vertebral artery in 6 of 30 (20%) and abundance of venous plexi prevented the proper exposure of C1 lateral mass and screw placement. Hypoglossal canal also had potential risk of injury during screw placement. CONCLUSION: In patients of C1A, when C1 lateral mass screw placement is programmed, factors limit its use should be well studied, and CT angiography is essential.