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Wei Zhang, Joseph A. DeMattia, Hua Song and William T. Couldwell

Object. Extensive invasion and angiogenesis are hallmark features of malignant gliomas. Communication between malignant glioma cells and surrounding astrocytes occurs, resulting in transformation of the astrocytic phenotype. In the present study, the authors examined whether malignant glioma cells and vascular endothelial cells (VECs) communicate through the formation of gap junctions and whether this communication influences angiogenesis.

Methods. Connexin43 (Cx43), a gap junction protein expressed in glioma cells, was identified in human umbilical VECs (HUVECs). Immunocytochemical staining for Cx43 demonstrated immunoreactive plaques at areas of cell—cell contact among HUVECs as well as between HUVECs and Cx43-expressing malignant glioma cells. Dye transfer, performed using the gap junction—permeable dye dicarboxy-dichlorofluorescein diacetate (CDCF), among these cocultures indicated that these were functional communications. Calcium signaling also occurred from malignant glioma cells to HUVECs. Tube formation by HUVECs cocultured with Cx43-transfected T98G malignant glioma cells (T98G-Cx43 cells) or with U87MG malignant glioma cells, which naturally express Cx43, was significantly increased compared with tube formation by HUVECs alone. The difference in tube formation by HUVECs cocultured with empty vector—transfected T98G glioma cells (T98G-mock cells) or with Cx43-deficient U373MG malignant glioma cells and tube formation by HUVECs alone was not statistically significant. Furthermore, the concentration of vascular endothelial growth factor (VEGF), an angiogenic factor important for the induction of angiogenesis and blood vessel formation, was significantly higher in medium harvested from cultures of T98G-Cx43 cells than in that harvested from cultures of control T98G-mock cells. Human malignant glioma U87MG cells also secreted increased concentrations of VEGF as compared with HUVECs alone. Nevertheless, there was no statistically significant difference in tube formation by HUVECs cultured in medium conditioned by either Cx43-expressing or Cx43-deficient glioma cells, suggesting that the direct gap junction communication between glioma cells and HUVECs may play a much more significant role than the increased VEGF secretion in vascular tube formation in this assay.

Conclusions. These results indicate that functional gap junction formation between human malignant glioma cells and VECs occurs. This communication appears to influence tumor angiogenesis. Targeting gap junction signaling may offer a potential mechanism for therapy in patients with these tumors.

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Wei Zhang, Chiedozie Nwagwu, Duc Minh Le, V. Wee Yong, Hua Song and William T. Couldwell

Object. Malignant glioma cells, similar to astrocytes, express connexin43 (Cx43) universally but at widely varied levels. Data from previous studies have demonstrated that malignant glioma cells form functional gap junction channels among themselves as well as with astrocytes and that such a communication has the potential to modulate the phenotypic characteristics of astrocytes. Recently, gap junctions have been demonstrated to play a role in the invasive phenotype of malignant gliomas. In this study, the authors have further investigated the motility and invasion ability of Cx43-overexpressing and Cx43-deficient malignant glioma cells.

Methods. Using a standard invasion system of a Matrigel transwell invasion chamber, the authors found that the number of Cx43-transfected C6 glioma cells (C6-Cx43 cells) migrating through the Matrigel-coated membrane was similar to that of mock-transfected control cells (C6-mock cells) during the first 24 hours, but increased significantly thereafter. When these cells were cocultured with astrocytes, the number of invading C6-Cx43 cells was more than threefold greater than the number of invading C6-mock cells. Results of an in vitro cell motility assay also demonstrated that C6-Cx43 cells were more motile and scatter-active than C6-mock cells. Furthermore, zymographic analysis of MMPs, an important determinant in glioma invasion, demonstrated that the amounts of MMP-2 and MMP-9 in culture medium collected from C6-Cx43 cells were orders of magnitude higher than those from C6-mock cells. In addition, BB-94, a synthetic MMP inhibitor, significantly inhibited C6-Cx43 cell invasion.

Conclusions. The overexpression of gap junction proteins in glioma cells and the intercellular communication between tumor and nontumor glia cells may play important roles in the facilitation of glioma cell invasion.

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Ya-Bin Ji, Yong-Ming Wu, Zhong Ji, Wei Song, Sui-Yi Xu, Yao Wang and Su-Yue Pan

Object

Intracarotid artery cold saline infusion (ICSI) is an effective method for protecting brain tissue, but its use is limited because of undesirable secondary effects, such as severe decreases in hematocrit levels, as well as its relatively brief duration. In this study, the authors describe and investigate the effects of a novel ICSI pattern (interrupted ICSI) relative to the traditional method (uninterrupted ICSI).

Methods

Ischemic strokes were induced in 85 male Sprague-Dawley rats by occluding the middle cerebral artery for 3 hours using an intraluminal filament. Uninterrupted infusion groups received an infusion at 15 ml/hour for 30 minutes continuously. The same infusion speed was used in the interrupted infusion groups, but the whole duration was divided into trisections, and there was a 20-minute interval without infusion between sections. Forty-eight hours after reperfusion, H & E and silver nitrate staining were utilized for morphological assessment. Infarct sizes and brain water contents were determined using H & E staining and the dry-wet weight method, respectively. Levels of neuron-specific enolase (NSE), S100β protein, and matrix metalloproteinase 9 (MMP-9) in the serum were determined using enzyme-linked immunosorbent assay. Neurological deficits were also evaluated.

Results

Histology showed that interrupted ICSI did not affect neurons or fibers in rat brains, which suggests that this method is safe for brain tissues with ischemia. The duration of hypothermia induced by interrupted ICSI was longer than that induced via the traditional method, and the decrease in hematocrit levels was less pronounced. There were no differences in infarct size or brain water content between uninterrupted and interrupted ICSI groups, but neuron-specific enolase and matrix metalloproteinase 9 serum levels were more reduced after interrupted ICSI than after the traditional method.

Conclusions

Interrupted ICSI is a safe method. Compared with traditional ICSI, the interrupted method has a longer duration of hypothermia and less effect on hematocrit and offers more potentially improved neuroprotection, thereby making it more attractive as an infusion technique in the clinic.

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Wei Qu, Dingjun Hao, Qining Wu, Zongrang Song and Jijun Liu

Unilateral facet dislocation at the subaxial cervical spine (C3–7) in children younger than 8 years of age is rare. The authors describe a surgical approach for irreducible subaxial cervical unilateral facet dislocation (SCUFD) at C3–4 in a 5-year-old boy and present a literature review. A dorsal unilateral approach was applied, and a biodegradable plate was used for postreduction fixation without fusion after failed conservative treatment. There was complete resolution of symptoms and restored cervical stability. Two years after surgery, the patient had recovered range of motion in C3–4. In selected cases of cervical spine injury in young children, a biodegradable plate can maintain reduction until healing occurs, obviate the need to remove an implant, and recover the motion of the injured segment.

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Song-Bai Gui, Sheng-Yuan Yu, Lei Cao, Ji-wei Bai, Xin-Sheng Wang, Chu-Zhong Li and Ya-Zhuo Zhang

OBJECTIVE

At present, endoscopic treatment is advised as the first procedure in cases of suprasellar arachnoid cysts (SSCs) with hydrocephalus. However, the appropriate therapy for SSCs without hydrocephalus has not been fully determined yet because such cases are very rare and because it is usually difficult to perform the neuroendoscopic procedure in patients without ventriculomegaly given difficulties with ventricular cannulation and the narrow foramen of Monro. The purpose of this study was to find out the value of navigation-guided neuroendoscopic ventriculocystocisternostomy (VCC) for SSCs without lateral ventriculomegaly.

METHODS

Five consecutive patients with SSC without hydrocephalus were surgically treated using endoscopic fenestration (VCC) guided by navigation between March 2014 and November 2015. The surgical technique, success rate, and patient outcomes were assessed and compared with those from hydrocephalic patients managed in a similar fashion.

RESULTS

The small ventricles were successfully cannulated using navigational tracking, and the VCC was accomplished in all patients. There were no operative complications related to the endoscopic procedure. In all patients the SSC decreased in size and symptoms improved postoperatively (mean follow-up 10.4 months).

CONCLUSIONS

Endoscopic VCC can be performed as an effective, safe, and simple treatment option by using intraoperative image-based neuronavigation in SSC patients without hydrocephalus. The image-guided neuroendoscopic procedure improved the accuracy of the endoscopic approach and minimized brain trauma. The absence of hydrocephalus in patients with SSC may not be a contraindication to endoscopic treatment.

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Haihui Jiang, Zhe Zhang, Xiaohui Ren, Wei Zeng, Junmei Wang and Song Lin

OBJECTIVE

1p/19q co-deletion is a well-established tumor cell–specific chromosomal abnormality in oligodendroglial tumors. The endothelial cells (ECs) of oligodendroglial tumor vessels are considered to be normal cells that do not acquire mutations.

METHODS

A total of 30 samples from 16 male and 14 female patients (median age of 46.5 years) with a histological diagnosis of primary anaplastic oligodendroglioma (AO) were collected in the study. The immunofluorescence technique was used to identify vascular ECs, and the 1p/19q status was detected with fluorescence in situ hybridization. Kaplan-Meier plots were compared using the log-rank method.

RESULTS

The ECs in AO had a higher 1p36 (detected signal) deletion rate than 1q25 (reference signal) (p < 0.01) and a higher 19q13 (detected signal) deletion rate than 19p13 (reference signal) (p < 0.01). The survival analysis results showed that both the progression-free survival (PFS) and overall survival (OS) of the patients with 1p/19q–co-deleted ECs were significantly longer than those with 1p/19q-intact ECs (PFS, p < 0.001; OS, p < 0.001). This correlation was validated by an independent cohort. In addition, the Cox regression model revealed that 1p/19q co-deletion in ECs was an independent prognostic factor (HR 0.056 [95% CI 0.012–0.261], p < 0.001 for PFS; HR 0.061 [95% CI 0.013–0.280], p < 0.01 for OS).

CONCLUSIONS

1p/19q co-deletion and polysomy can be also found in the ECs of AO, which suggests that the ECs are, in part, tumor related and reflect a novel aspect of tumor angiogenesis.

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Junxiang Wen, Yingchao Han, Song Guo, Mingjie Yang, Lijun Li, Guixin Sun, Jun Wang, Fangqiong Hu, Jing Liang, Li Wei, Qi Zhou, Weibin Zhang and Jun Tan

The authors studied restoration of respiratory function in rabbits, using the recurrent laryngeal nerve to restore function after the phrenic nerve had been severed. The results of this animal study are encouraging and suggest that a similar technique could possibly be used to help patients with severe cervical spinal cord injuries.

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Feng Zhou, Zixiao Yang, Wei Zhu, Liang Chen, Jianping Song, Kai Quan, Sichen Li, Peiliang Li, Zhiguang Pan, Peixi Liu and Ying Mao

OBJECTIVE

Epidermoid cysts of the cavernous sinus (CS) are rare, and no large case series of these lesions has been reported. In this study, the authors retrospectively reviewed the outcomes of the surgical management of CS epidermoid cysts undertaken at their center and performed a review of any such cysts reported in the literature over the past 40 years.

METHODS

Clinical data were obtained on 31 patients with CS epidermoid cysts that had been surgically treated at the authors’ hospital between 2001 and 2016. The patients’ medical records, imaging data, and follow-up outcomes were retrospectively analyzed. The related literature from the past 40 years (18 articles, 20 patients) was also evaluated.

RESULTS

The most common chief complaints were facial numbness or hypesthesia (64.5%), absent corneal reflex (45.2%), and abducens or oculomotor nerve deficit (35.5%). On MRI, 51.6% of the epidermoid cysts showed low T1 signals and equal or high T2 signals. In the other lesions, the radiological findings varied considerably given differences in the composition of the cysts. Surgery was performed via the extradural approach (58.1%), intradural approach (32.3%), or a combined approach (9.7%). After the operation, symptoms remained similar or improved in 90.3% of patients and new oculomotor paralysis developed after the operation in 9.7% of patients. Seven patients (22.6%) developed meningitis postoperatively (5 aseptic and 2 septic), and all of them recovered. All patients achieved good recovery before discharge (Karnofsky Performance Status score ≥ 70). Over an average follow-up of 4.6 ± 3.0 years in 25 patients (80.6%), no recurrence or reoperation occurred, regardless of whether total or subtotal resection of the capsule had been achieved.

CONCLUSIONS

Both the extradural and intradural approaches can enable satisfactory lesion resection. A favorable prognosis and symptomatic improvement can be expected after both total and subtotal capsule resections. Total capsule resection is encouraged to minimize the possibility of recurrence provided that the resection can be safely performed.