Trans-eyebrow supraorbital keyhole approach in suprasellar and third ventricular craniopharyngioma surgery: the experience of 27 cases and a literature review.

BACKGROUND: The trans-eyebrow supraorbital keyhole approach, a minimal transcranial approach, has been widely used in different types of surgery for sellar and parasellar lesions. In this study, we investigated the outcome of this approach in the surgical treatment of suprasellar and third ventricular craniopharyngioma. METHODS: Twenty-seven patients with suprasellar and third ventricular craniopharyngioma underwent surgery via a supraorbital approach between June 2007 and June 2018. The medical data and follow-up results were retrospectively analyzed. RESULTS: All tumors were located in the suprasellar region and the third ventricle. The mean tumor size was 29.1 mm. The mean follow-up period was 49.6 months. Gross total resection (GTR) was achieved in 23 patients (85.2%). Of 17 patients with preoperative visual impairment, 12 patients (70.6%) showed improvement. Following surgery, 11 patients exhibited new-onset anterior hypopituitarism, ten developed diabetes insipidus, and two became overweight. One residual tumor relapsed 1 year after surgery. No perioperative death, cerebrospinal fluid (CSF) rhinorrhea, or meningitis occurred. All patients exhibited satisfactory cosmetic results. At the last follow-up, the Extended Glasgow Outcome Scale Score was 8 in 25 patients (92.6%). CONCLUSION: The supraorbital trans-eyebrow keyhole approach is characterized by minimal invasion and a satisfactory cosmetic outcome. According to our experience, craniopharyngiomas located in the suprasellar region and the third ventricle can be safely resected via a trans-eyebrow supraorbital keyhole approach.

Comparison of the Effects of BMSC-derived Schwann Cells and Autologous Schwann Cells on Remyelination Using a Rat Sciatic Nerve Defect Model.

Schwann cells (SCs) are primarily responsible for the formation of myelin sheaths, yet bone marrow mesenchymal stem cell (BMSC)-derived SCs are often used to replace autologous SCs and assist with the repair of peripheral nerve myelin sheaths. In this study, the effects of the two cell types on remyelination were compared during the repair of peripheral nerves. Methods: An acellular nerve scaffold was prepared using the extraction technique. Rat BMSCs and autologous SCs were extracted. BMSCs were induced to differentiate into BMSC-derived SCs (B-dSCs) in vitro. Seed cells (BMSCs, B-dSCs, and autologous SCs) were cocultured with nerve scaffolds (Sca) in vitro. Rats with severed sciatic nerves were used as the animal model. A composite scaffold was used to bridge the broken ends. After surgery, electrophysiology, cell tracking analyses (EdU labeling), immunofluorescence staining (myelin basic protein (MBP)), toluidine blue staining, and transmission electron microscopy were conducted to compare remyelination between the various groups and to evaluate the effects of the seed cells on myelination. One week after transplantation, only a small number of B-dSCs expressed MBP, which was far less than the proportion of MBP-expressing autologous SCs (P<0.01) but was higher than the proportion of BMSCs expressing MBP (P<0.05). Four weeks after surgery, the electrophysiology results (latency time, conductive velocity and amplitude) and various quantitative indicators of remyelination (thickness, distribution, and the number of myelinated fibers) showed that the Sca+B-dSC group was inferior to the Sca+autologous SC group (P<0.05) but was superior to the Sca+BMSC group (P<0.05). Conclusions: Within 4 weeks after surgery, the use of an acellular nerve scaffold combined with B-dSCs promotes remyelination to a certain extent, but the effect is significantly less than that of the scaffold combined with autologous SCs.

Xenogeneic acellular nerve scaffolds supplemented with autologous bone marrow-derived stem cells promote axonal outgrowth and remyelination but not nerve function.

Autologous nerves, artificial scaffolds or acellular nerve scaffolds are commonly used in bridging treatment for peripheral nerve defects. Xenogeneic acellular nerve scaffolds and allogeneic cellular nerve scaffolds have the same structural characteristics. Due to the wider source of raw materials, these latter scaffolds have high-potential value for applications. However, whether their heterogeneity will affect nerve regeneration is unknown. The current study evaluated the efficiency of xenogeneic acellular nerve scaffolds (XANs) combined with 5-ethynyl-2'-deoxyuridine (EdU)-labeling of autologous bone marrow-derived stem cells (BMSCs) for repair of a 1.5 cm gap in rat sciatic nerves. XANs from rabbit tibial nerves were prepared, the structure and components of the scaffolds were evaluated after completely removing the cellular components. Animals were divided into four groups based on graft: the simple XAN group, the XAN + BMSC group, the XAN + Media (from BMSC culture) group, and the autograft group. Serological immune tests showed that XANs induce an immune response in the first 2 weeks after transplantation. Moreover, cell tracking revealed that the proportion of EdU+ cells decreased over time, as shown by the measures at 2 days (70%), 4 days (20%), and 8 days (even <3%) postoperatively. Nerve functional analyses revealed that in contrast to the autograft group results, the XAN-BMSC, XAN + Media, and XAN groups did not exhibit good restoration of the sciatic functional index (SFI) or electrophysiological results (the peak action potential amplitudes) 12 weeks, postoperatively. However, the XAN-BMSC and autograft groups demonstrated greater remyelination and increased axon numbers and myelin thickness than the XAN + Media and XAN groups 12 weeks, postoperatively (p < .05). In conclusion, in the early stage of transplantation, XANs induce a certain degree of inflammation. Although the combination of XANs with autologous BMSCs enhanced the number of regenerated axons and the remyelination, the combination did not effectively improve the recovery of nervous motor function. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 3065-3078, 2018.

Knockdown of long non-coding RNA AFAP1-AS1 inhibits growth and promotes apoptosis in pituitary adenomas.

Recent studies have reported that the long non-coding RNA (lncRNA) AFAP antisense RNA 1 (AFAP1-AS1) is involved in various biological processes and plays a key role in regulating cancer growth and metastasis in humans. However, its effects on tumorigenesis in pituitary adenomas remain unclear. The present study investigated the expression and biological role of AFAP1-AS1 in pituitary adenomas. We observed that the expression of AFAP1-AS1 was considerably higher in the pituitary adenoma tissues as compared to its expression in the adjacent tissues. Additionally, knockdown of AFAP1-AS1 inhibited the proliferation, arrested the cell cycle in the G1-to-S transition phase, and promoted apoptosis in GH3 and MMQ cells. Finally, knockdown of AFAP1-AS1 also promoted the expression of PTEN and inhibited the expression of PI3K and p-AKT. Our results provided novel insights into the function and mechanism of action of AFAP1-AS1 in the pathogenesis of pituitary adenomas.

Carotid-Carotid Artery Crossover Bypass with a Synthetic Vascular Graft for Symptomatic Type 1A Common Carotid Artery Occlusion.

OBJECTIVE: To investigate the effect of carotid-carotid artery crossover bypass with a synthetic vascular graft for symptomatic type 1A common carotid artery occlusion (CCAO). METHODS: A retrospective analysis was conducted of patients with symptomatic type 1A CCAO who underwent carotid-carotid artery crossover bypass surgery via a retropharyngeal route with a synthetic vascular graft in the Department of Neurosurgery at our hospital. Preoperative demographic data, surgical complications, incidence of stroke during follow-up, and other clinical data were summarized. RESULTS: Between 2011 and 2016, carotid-carotid artery crossover bypass was performed with a synthetic vascular graft in 4 patients with type 1A CCAO. The mean patient age was 63.3 years (range, 49-69 years). Clinical symptoms included dizziness, amaurosis fugax, persistent limb numbness, and transient ischemic attack. In all 4 patients, postoperative computed tomography angiography showed internal carotid artery thickening due to successful bypass, whereas computed tomography perfusion showed improved postoperative cerebral perfusion on the side of the lesion. The sole perioperative complication was a complaint of foreign body sensation on swallowing in 1 patient. The mean duration of follow-up was 40.3 months (range, 14-77 months), during which no newly occurred cerebral ischemia or synthetic vascular graft occlusion was observed. CONCLUSIONS: Carotid-carotid artery crossover bypass with a synthetic vascular graft is a safe and effective therapeutic approach for patients with symptomatic type 1A CCAO. However, studies with larger series are needed to enable more precise conclusions.

Microsurgical Resection of Cervical Spinal Cord Arteriovenous Malformations: Report of 6 Cases.

OBJECTIVE: To summarize the experience in microsurgical resection of cervical spinal cord arteriovenous malformation (AVM). METHODS: Six patients undergoing microsurgical resection of cervical intramedullary AVM in the Third Affiliated Hospital of Sun Yat-sen University, China, between March 2005 and March 2015 were reviewed retrospectively, and their clinical manifestations, imaging data, surgical treatment, and results of long-term follow-up were analyzed. RESULTS: Of the 6 patients who underwent AVM resection, 2 had compact AVMs and 4 had diffuse AVMs. All 6 patients were reexamined with spinal magnetic resonance imaging within 48 hours after surgery, and 1 patient was examined with digital subtraction angiography. The average patient age was 40.7 ± 10.4 years (range, 29-60 years). Three patients had chronic onset, of whom 2 developed sensory disturbances and 1 had muscle weakness. The other 3 patients had acute onset, including 1 with sudden quadriplegia, 1 with idiopathic severe headache and altered consciousness, and 1 with idiopathic neck pain. The average duration of follow-up was 48.5 ± 38.9 months (range, 15-119 months). One patient experienced complete recovery, and the other 5 patients showed improvement. No patient exhibited deterioration. CONCLUSION: Microsurgical resection of cervical intramedullary AVMs has obtained satisfactory clinical results. Preoperative magnetic resonance angiography, computed tomography angiography, and digital subtraction angiography are useful for evaluating the angioarchitecture, which is key to the success of surgery. Intraoperative indocyanine green fluorescence angiography is an important aid in the surgical treatment of spinal AVMs.

NF-κB induces miR-148a to sustain TGF-ß/Smad signaling activation in glioblastoma.

BACKGROUND: Inflammatory cytokines and transforming growth factor-ß (TGF-ß) are mutually inhibitory. However, hyperactivation of nuclear factor-κB (NF-κB) and TGF-ß signaling both emerge in glioblastoma. Here, we report microRNA-148a (miR-148a) overexpression in glioblastoma and that miR-148a directly suppressed Quaking (QKI), a negative regulator of TGF-ß signaling. METHODS: We determined NF-κB and TGF-ß/Smad signaling activity using pNF-κB-luc, pSMAD-luc, and control plasmids. The association between an RNA-induced silencing complex and QKI, mitogen-inducible gene 6 (MIG6), S-phase kinase-associated protein 1 (SKP1), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA was tested with microribonucleoprotein immunoprecipitation and real-time PCR. Xenograft tumors were established in the brains of nude mice. RESULTS: QKI suppression induced an aggressive phenotype of glioblastoma cells both in vitro and in vivo. Interestingly, we found that NF-κB induced miR-148a expression, leading to enhanced-strength and prolonged-duration TGF-ß/Smad signaling. Notably, these findings were consistent with the significant correlation between miR-148a levels with NF-κB hyperactivation and activated TGF-ß/Smad signaling in a cohort of human glioblastoma specimens. CONCLUSIONS: These findings uncover a plausible mechanism for NF-κB-sustained TGF-ß/Smad activation via miR-148a in glioblastoma, and may suggest a new target for clinical intervention in human cancer.

Clipping of anterior communicating artery aneurysms in the early post-rupture stage via transorbital keyhole approach--Chinese neurosurgical experience.

The anterior communicating artery (AComA) complex is the site at which intracranial aneurysms occur most frequently. At present, effective treatments for AComA aneurysms are yet to be developed. Here, we present our experience in successfully managing AComA aneurysms via the transorbital keyhole approach. A total of 52 patients having a history of aneurysm rupture received surgery. All patients were assigned a Hunt-Hess grade prior to surgery. The cistern was opened to expose the AComA complex using a keyhole approach, and aneurysms were then surgically clipped with the assistance of neuroendoscopy or indocyanine green angiography. Surgery outcomes were confirmed using computed tomography angiography (CTA). Each of the 52 AComA aneurysms was successfully clipped with a single operation. Three of these patients experienced intraoperative aneurysm rupture. Five had postoperative hydrocephalus which was successfully treated with ventriculoperitoneal shunt. All patients survived the surgical procedure. Using the Glasgow Outcome Scale scores for evaluation, 39 patients (75.0%) had good recovery, 9 (17.3%) had moderate disability, 2 (3.8%) had severe disability, and 2 patients who had been in preoperative comas (3.8%) remained in a vegetative state. During the follow-up period, CTA showed no recurrence of rupture or bleeding in all cases. Results of logistic analysis indicated that the transorbital keyhole approach was feasible based on the patients' preoperative Hunt-Hess grades, which should be considered a priority in using this approach in the treatment of ruptured AComA aneurysms.

Intraoperative Ultrasonography Combined with Indocyanine Green Video-Angiography in Patients with Cerebral Arteriovenous Malformations.

BACKGROUND AND PURPOSE: During the operation, accurately identifying the boundary of cerebral arteriovenous malformation (AVM) and discriminating between feeding arteries and draining veins is the key to successful surgical treatment of cerebral AVM. We evaluated the application of intraoperative ultrasonography (IOU) combined with intraoperative indocyanine green video-angiography (IOICGA) in the patients with cerebral AVM. METHODS: The effects of IOU combined with IOICGA on AVM surgery were observed in 12 patients with cerebral AVM. RESULTS: The lesions of cerebral AVM were completely removed in the 12 patients. IOU could clearly visualize the boundary of AVM, so no patients had massive hemorrhage caused by rupture of malformed vessels. IOU also could detect the location of deep vessels and a total of 11 deep vessels were identified in the 12 patients. IOICGA was performed 41 times altogether in the 12 patients, and 31 feeding arteries and 10 draining veins were identified, so there was no massive hemorrhage caused by misjudgment of feeding arteries or draining veins. CONCLUSIONS: IOU combined with IOICGA can identify the boundary of AVM, detect deep vessels, and discriminate between feeding arteries and draining veins, reducing operation difficulty, decreasing mortality and disability rate, and increasing the rate of complete excision.

Prevalence and fluoroquinolone resistance of pseudomonas aeruginosa in a hospital of South China.

Pseudomonas aeruginosa is an opportunistic pathogen that poses a threat in clinical settings. This study aimed to investigate the molecular characterization and epidemiology of fluoroquinolones (FQs) resistance in P. aeruginosa isolated from South China. A total of 256 P. aeruginosa strains isolated from outpatients, emergency patients and inpatients were collected from January 2010 to December 2010 in the hospital of South China. The resistance profile of all isolated strains was screened by antibiotic-susceptibility testing, and the molecular characteristics of plasmid-mediated quinolone resistance (PMQR) and the quinolone resistance determining region (QRDR) were determined using PCR in combination with DNA sequencing. The result of antibiotic-susceptibility tests showed that most strains were sensitive to polymyxin B, piperacillin, piperacillin/tazobactam, ceftazidime and amikacin. Moreover, 65 isolates were identified as resistant to ciprofloxacin. Further analysis of QRDR revealed that the resistant strains carried at least one mutation in the gyrA (The83Ile), gyrB (Ser467Phe, Gln468His) and parC (Ser87Leu) genes, but no mutation was detected in parE. For the first time, we report here that the qnrA1 gene is associated with low levels of resistance to ciprofloxacin from clinical P. aeruginosa isolates in South China. The mutation of gyrA (at position 83) is clearly linked to the FQs resistance of P. aeruginosa. Moreover, FQs resistance of P. aeruginosa may be due to the chromosome-mediated resistance mechanism rather than PMQR.

On clipping of anterior communicating artery aneurysm via eyebrow-lateral keyhole approach.

OBJECTIVE: To evaluate the application of eyebrow-lateral keyhole approach in clipping of anterior communicating artery aneurysm (ACAA) through observing the therapeutic effect of eyebrow-lateral keyhole approach on ACAA. METHODS: In 37 patients with ACAA, cisterns were exposed via the eyebrow-lateral keyhole approach to reveal ACAA complex followed by clipping of ACAA. Of the 37 patients, external ventricular drainage was performed on 5 patients before microsurgery. All patients underwent head CT angiography on the second day after operation. RESULTS: Clipping of ACAA was successful in all patients at the first time. In 3 patients, ruptured aneurysm occurred during operation. Three patients underwent ventriculoperitoneal shunt because of postoperative hydrocephalus. Two patients had one-sided anterior cerebral artery infarction after operation. No patient died during operation. Follow-up after the operation indicated that 26 patients returned to normal life and work, 6 patients were able to look after themselves, 4 patients required care in their daily life and one patient died. CONCLUSION: The eyebrow-lateral keyhole approach is a preferred choice for surgical treatment of ACAA because it can cope with brain swelling and intraoperative ruptured aneurysm. However, it has a certain range of application, so we must strictly follow its indications.

Glioma-derived ADAM10 induces regulatory B cells to suppress CD8+ T cells.

CD8+ T cells play an important role in the anti-tumor activities of the body. The dysfunction of CD8+ T cells in glioma is unclear. This study aims to elucidate the glioma cell-derived ADAM10 (A Disintegrin and metalloproteinase domain-containing protein 10) in the suppression of CD8+ effector T cells by the induction of regulatory B cells. In this study, glioma cells were isolated from surgically removed glioma tissue and stimulated by Phorbol myristate acetage (PMA) in the culture. The levels of ADAM10 in the culture were determined by enzyme-linked immunosorbent assay. Immune cells were assessed by flow cytometry. The results showed that the isolated glioma cells express ADAM10, which was markedly up regulated after stimulated with PMA. The glioma-derived ADAM10 induced activated B cells to differentiate into regulatory B cells, the later suppressed CD8+ T cell proliferation as well as the induced regulatory T cells, which also showed the immune suppressor effect on CD8+ effector T cell proliferation. In conclusion, glioma cells produce ADAM10 to induce Bregs; the latter suppresses CD8+ T cells and induces Tregs.

Effects of cerebral microvascular endothelial cells and vascular endothelial growth factor on the proliferation and differentiation of NSCs: a comparative study.

In adult mammalian brain, microvessels may produce a special microenvironment and then influence the characteristics of neural stem cells (NSCs). This work aims to compare the effects of cerebral microvascular endothelial cells (CMECs) and vascular endothelial growth factor (VEGF) on the behaviors of NSCs. An in vitro model with co-cultured CMECs and NSCs was established by using transwell co-culture system. The expression of nestin and NF in the early stage of the co-culture, and NF in the later stage were explored by immunostaining. Results demonstrate that both CMECs and VEGF stimulate the proliferation of NSCs and inhibit the differentiation. After removing CMECs or VEGF from the co-culture system, a further culture in medium for the differentiation of NSCs was performed. The percentage of NF-positive cells in the CMECs co-culture group is the highest, suggesting the improved neuronal differentiation of NSCs by CMECs.

Correlation of MMP(1) and TIMP (1) expression with pituitary adenoma fibrosis.

OBJECTIVE: To explore the correlation of matrix metalloproteinase-1 (MMP(1)) and tissue inhibitor of metalloproteinase-1 (TIMP(1)) with pituitary adenoma fibrosis. METHODS: Thirty-eight pituitary adenoma specimens were divided into fibrous group (6 patients) and non-fibrous group (32 patients). MMP(1) and TIMP(1) expression was detected by RT-PCR and immunohistochemistry. The collagen content was determined by Sirius scarlet staining. RESULTS: In fibrous and non-fibrous group: (1) the collagen content was 20.95 +/- 8.42% and 7.98 +/- 5.18% respectively, and there was a statistical significance (P < 0.01). (2) The expression of MMP(1)mRNA was 0.47 +/- 0.40 and 0.59 +/- 0.54 respectively and its protein expression was 0.12 +/- 0.09 and 0.13 +/- 0.09 respectively, and there was no statistical significance (P > 0.05). Their expression was not related to collagen content (P > 0.05). (3) The expression of TIMP(1)mRNA was 1.61 +/- 1.09 and 0.79 +/- 0.59 respectively and its protein expression was 0.58 +/- 0.11 and 0.32 +/- 0.18 respectively, and there was a statistical significance (P < 0.01). Their expression was related to collagen content (P < 0.01). CONCLUSION: The pathological features of pituitary adenoma fibrosis are excessive collagen deposition. High expression of TIMP(1) may be an important cause.

Proliferation and neurogenesis of neural stem cells enhanced by cerebral microvascular endothelial cells.

In adult mammalian brain, vascular cells reside throughout life, close to central nervous system germinal zones, and neural stem cells (NSCs) mainly localize in the dentate gyrus of the hippocampus, subventricular zone, and olfactory bulb. Microvessels appear to produce a special microenvironment that may influence the characteristics of NSCs. To explore this potential correlation, an in vitro model with cocultured cerebral microvascular endothelial cells (CMECs) and NSCs was established in our study by using a transwell coculture system. The expression of nestin and NF in the early stage of coculture, and NF in the late stage, was detected by immunostaining. The results demonstrated that CMECs can stimulate self-renewal of NSCs and inhibit their differentiation, implying the potential of CMECs in promoting the neural differentiation of NSCs.

Electrospun nanofibers immobilized with collagen for neural stem cells culture.

Fibrous mats via electrospinning have been widely applied in tissue engineering. In this work, nanofibers were prepared via electrospinning from polymer with different content of carboxyl groups. A natural material, collagen, was then immobilized onto the nanofiber surface by N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC)/N-Hydroxysuccinimide (NHS) activation process. It was found that the immobilization degree of collagen could be facilely modulated. The obtained collagen-modified nanofibers were used for neural stem cells culture, and unmodified nanofibers were used as a control. Results indicated that the modification of collagen could enhance the attachment and viability of the cultured neural stem cells.