Two-point fixation enhanced the outcome of laparoscopy-assisted ventriculoperitoneal shunt in adult patients with hydrocephalus: a retrospective study.

Objective: In patients with hydrocephalus, laparoscopy significantly improved ventriculoperitoneal shunt (VPS) outcomes. However, abdominal complications still occur, which require revision surgeries. In this study, we aimed to examine whether laparoscopy-assisted VPS with two-point fixation (LAVPS-TPF) has better outcomes than those of VPS (open-VPS) and laparoscopy-assisted VPS with no fixation (LAVPS-NF). Methods: We retrospectively reviewed clinical records of 105 open-VPS, 40 LAVPS-NF, and 49 LAVPS-TPF cases from 2015 to 2020. Data including body mass index, etiology, abdominal surgery history, Glasgow coma scale (GCS), operation time, in-hospital days, shunt failure, complications, and modified Rankin scores were analyzed, as well as subgroups of patients with history of abdominal surgery, GCS scores, and revision surgeries. Results: The LAVPS-TPF group demonstrated decreased shunt failure rates at 12 months (2.04%) compared to those of the open-VPS group (14.29%, P = 0.020) and reduced abdominal shunt-related complications (P = 0.004 vs. open-VPS and LAVPS-NF) and shunt revisions. In the LAVPS-TPF group with abdominal history (n = 51), 12-month shunt failure rates (P = 0.020 vs. open-VS), repair frequency (P = 0.020 vs. open-VS), and abdominal complications (P = 0.003 and 0.006 vs. open-VS and LAVPS-NF) were reduced. In the LAVPS-TPF group with GCS scores of 13-15 (n = 152), shunt failure rates at 12 months, abdominal complications, and revision frequency were decreased (P < 0.05 vs. other groups). Compared to the LAVPS-NF group, neurological complications were also reduced (P = 0.001). Among revision surgeries (n = 28), fixed shunts resulted in improved shunt survival rates at 12 months, reduced abdominal complications, and secondary revisions (P < 0.05). Moreover, a more optimal recovery without neurological sequelae was achieved by shunt fixation than that by LAVPS-NF (P < 0.01). Conclusions: LAVPS-TPF significantly improved shunt survival rates at 12 months and reduced the incidence of abdominal shunt-related complications compared to open-VPS and LAVPS-NF, especially in patients with history of abdominal surgery, higher GCS scores, and revision surgeries. However, further studies are required to confirm these benefits.

Impact of vitamin D on the prognosis after spinal cord injury: A systematic review.

Vitamin D (VitD) insufficiency is a worldwide health problem and affects billions of people. Spinal cord injury (SCI) patients seem more susceptible to developing suboptimal levels of VitD. However, the literature regarding its impact on the prognosis of SCI is limited. Thus, in this review, we systematically investigated the published studies via a combination of keywords associated with SCI and VitD in four medical databases (Medline, Embase, Scopus, and Web of Science). All included studies were analyzed, and selected clinical data on the prevalence of VitD insufficiency (serum 25-hydroxyvitamin D < 30 ng/ml) and deficiency (serum 25-hydroxyvitamin D < 20 ng/ml) were collected for further meta-analysis via random effects. Through literature review, a total of 35 studies were eligible and included. The meta-analysis of VitD status (13 studies, 1,962 patients) indicated high prevalence of insufficiency (81.6% [75.7, 87.5]) and deficiency (52.5% [38.1, 66.9]) after SCI. Besides, low levels of VitD were reported to be associated with a higher risk of skeletal diseases, venous thromboembolism, psychoneurological syndromes, and chest illness after injury. Existing literature suggested that supplemental therapy might act as an adjuvant treatment to facilitate post-injury rehabilitation. Non-human experimental studies highlighted the neuroprotective effect of VitD, which was associated with enhancing axonal and neuronal survival, suppressing neuroinflammation, and modulating autophagy. Therefore, the current evidence suggests that the prevalence of VitD insufficiency is high in the SCI population, and low-level VitD may impair functional restoration after SCI. VitD supplemental treatment may have potential benefits to accelerate rehabilitation in mechanistically related processes after SCI. However, due to the limitation of the available evidence, more well-designed randomized controlled trials and mechanism experimental research are still needed to validate its therapeutic effect, elucidate its neuroprotective mechanism, and develop novel treatments.

Neural Stem Cells Overexpressing Nerve Growth Factor Improve Functional Recovery in Rats Following Spinal Cord Injury via Modulating Microenvironment and Enhancing Endogenous Neurogenesis.

Spinal cord injury (SCI) is a devastating event characterized by severe motor, sensory, and autonomic dysfunction. Currently, there is no effective treatment. Previous studies showed neural growth factor (NGF) administration was a potential treatment for SCI. However, its targeted delivery is still challenging. In this study, neural stem cells (NSCs) were genetically modified to overexpress NGF, and we evaluated its therapeutic value following SCI. Four weeks after transplantation, we observed that NGF-NSCs significantly enhanced the motor function of hindlimbs after SCI and alleviated histopathological damage at the lesion epicenter. Notably, the survival NGF-NSCs at lesion core maintained high levels of NGF. Further immunochemical assays demonstrated the graft of NGF-NSCs modulated the microenvironment around lesion core via reduction of oligodendrocyte loss, attenuation of astrocytosis and demyelination, preservation of neurons, and increasing expression of multiple growth factors. More importantly, NGF-NSCs seemed to crosstalk with and activate resident NSCs, and high levels of NGF activated TrkA, upregulated cAMP-response element binding protein (CREB) and microRNA-132 around the lesion center. Taken together, the transplantation of NGF-NSCs in the subacute stage of traumatic SCI can facilitate functional recovery by modulating the microenvironment and enhancing endogenous neurogenesis in rats. And its neuroprotective effect may be mediated by activating TrkA, up-regulation of CREB, and microRNA-132.

COL5A1 Serves as a Biomarker of Tumor Progression and Poor Prognosis and May Be a Potential Therapeutic Target in Gliomas.

Glioma is the most common malignancy of the central nervous system. Although advances in surgical resection, adjuvant radiotherapy, and chemotherapy have been achieved in the last decades, the prognosis of gliomas is still dismal. COL5A1 is one of the collagen members with minor content but prominent functions. The present study examined the biological functions, prognostic value, and gene-associated tumor-infiltrating immune cells of COL5A1 through experiments and bioinformatics analysis. We found that the overexpression of COL5A1 was positively correlated with the increasing tumor malignancies and indicated poor prognosis in gliomas. Moreover, downregulation of COL5A1 could inhibit proliferation and migration of glioma cells and enhance their temozolomide sensitivities in vitro. Further bioinformatic analysis revealed that COL5A1 and its co-expressed genes participated in a number of pathways and biological processes involved in glioma progression. Finally, we evaluated the tumor-infiltrating immune cells of gliomas depending on COL5A1 and found that the percentages of the dendritic cells, which were known as the central mediator of tumor microenvironment in gliomas, were positively associated with the expression levels of COL5A1. Taken together, COL5A1 is an important biomarker and potential therapeutic target of gliomas.

Current Understanding of Hearing Loss in Sporadic Vestibular Schwannomas: A Systematic Review.

OBJECTIVE: Hearing loss is the most common initial symptom in patients with sporadic vestibular schwannomas (SVS). Hearing preservation is an important goal of both conservative and surgical therapy. However, the mechanism of SVS-associated hearing loss remains unclear. Thus, we performed this systematic review to summarize the current understanding of hearing loss in the SVS and distill a testable hypothesis to further illuminate its underlying mechanism. METHODS: A systematic review querying four databases (PubMed, Medline, Embase, and Web of Science) was performed to identify studies evaluating hearing loss in patients with SVS and exploring the potential mechanisms of hearing impairment. RESULTS: A total of 50 articles were eligible and included in this review. After analysis, the retrieved studies could be categorized into four types: (1) 29 studies explore the relationship between hearing loss and the growth pattern of the tumor (e.g., tumor size/volume, growth rate, tumor location, etc.); (2) ten studies investigate the potential role of cochlear dysfunction in hearing deterioration, including structural abnormality, protein elevation in perilymph, and cochlear malfunctioning; (3) two studies looked into SVS-induced impairment of auditory pathway and cortex; (4) in the rest nine studies, researchers explored the molecular mechanism underlying hearing loss in SVS, which involves molecular and genetic alterations, inflammatory response, growth factors, and other tumor-associated secretions. CONCLUSIONS: Multiple factors may contribute to the hearing impairment in SVS, including the growth pattern of tumor, cochlear dysfunction, impairment of auditory pathway and cortex, genetic and molecular changes. However, our current understanding is still limited, and future studies are needed to explore this multifactorial hypothesis and dig deeper into its underlying mechanism.

Efficacy of unilateral hemilaminectomy for intraspinal tumor resection: a systematic review and meta-analysis.

BACKGROUND: To evaluate, via a meta-analysis, the clinical effect of unilateral hemilaminectomy for intraspinal tumor removal. METHODS: PubMed, Springer, Wanfang Data, CBM, CNKI, and other databases were searched for relevant randomized controlled trials (RCT), in Chinese and other languages, that involved comparisons of unilateral hemilaminectomy with other techniques for intraspinal tumor removal. RESULTS: Thirteen RCTs were finally included, with a total of 1,424 patients. Unilateral hemilaminectomy for intraspinal tumor removal was found to reduce the amount of intraoperative hemorrhage (Z =45.67, P<0.00001), operative time (Z =55.35, P<0.00001), length of hospital stay (Z =111.67, P<0.00001), and inbed time (Z =142.08, P<0.00001) of patients. Compared with the traditional operative methods, unilateral hemilaminectomy for intraspinal tumor removal can improve the cure rate of patients [odds ratio (OR) =3.84; 95% confidence interval (CI), 2.1-7.01; Z =4.38; P<0.001) and reduce the incidence of spinal deformities (OR =0.11; 95% CI, 0.04-0.34; Z =3.83; P=0.001). It does not increase the risks of postoperative cerebrospinal fluid leak (OR =0.63; 95% CI, 0.21-1.88; Z =0.82; P=0.41), postoperative infection (OR =0.74; 95% CI, 0.31-1.77; Z =0.67; P=0.50), pain (OR =0.29; 95% CI, 0.07-1.18; Z =1.73; P=0.08), myasthenia (OR =-0.04; 95% CI, -0.07 to 0.01; Z =2.29; P=0.02), and other complications. CONCLUSIONS: Unilateral hemilaminectomy for the microsurgical removal of intraspinal tumors has the advantages of minimal operative trauma, fast recovery, and better postoperative stability of the vertebral column.

Accuracy of ADC derived from DWI for differentiating high-grade from low-grade gliomas: Systematic review and meta-analysis.

OBJECTIVE: Quantitative apparent diffusion coefficient (ADC) values of diffusion weighted imaging (DWI) could be applied to grade gliomas. This meta-analysis was conducted to assess the accuracy of ADC analysis in differentiating high-grade (HGGs) from low-grade gliomas (LGGs). METHODS: PubMed, Cochrane library, Science Direct, and Embase were searched to identify suitable studies up to September 1, 2018. The quality of studies was evaluated by the quality assessment of diagnostic accuracy studies (QUADAS 2). We estimated the pooled sensitivity, specificity, positive and negative likelihood ratios (LR), diagnostic accuracy ratio (DOR) with 95% confidence intervals (CI), and determined the accuracy of the data by using the summary receiver operating characteristic (SROC) and calculating the area under the curve (AUC) to identity the accuracy of ADC analysis in grading gliomas. RESULTS: Eighteen studies including 1172 patients were included and analyzed. The pooled sensitivity, specificity, PLR, NLR, DOR, and AUC with 95% CIs of DWI with b values of 1000 s/mm for separating HGGs from LGGs were 0.81 (95% CI 0.75-0.86), 0.87 (95% CI 0.81-0.91), 6.1 (95% CI 4.2-8.9), 0.22 (95% CI 0.17-0.29), 28 (95% CI 17-45), and 0.91 (95% CI 0.88-0.93), respectively. DWI with b values of 3000 s/mm showed slightly higher accuracy than that of 1000 (sensitivity 0.80, specificity 0.90 and AUC 0.92). Meta-regression analyses showed that field strengths and b values had significant impacts on diagnostic efficacy. Deeks testing confirmed no significant publication bias in all studies. CONCLUSIONS: This meta-analysis suggested that ADC analysis of DWI have high accuracy in differentiating HGGs from LGGs. Standardized methodology is warranted to guide the use of this technique for clinical decision-making.

An Analysis of Clinical Efficacy of Microsurgical Resection of Intradural Neoplasm by Unilateral Approach with Caspar Retractors.

OBJECTIVE: This study aims to investigate the clinical efficacy of minimally invasive microsurgical resection of intraspinal tumors with the aid of Caspar retractors. MATERIALS AND METHODS: A total of 125 intraspinal tumor patients with lesions smaller than 6 cm, who were treated at the Neurosurgery Department of our hospital from March 2010 to March 2016, were retrospectively analyzed. Among these, 73 patients underwent microsurgical resection of intraspinal tumors with the aid of Caspar retractors, while 52 patients underwent conventional laminectomy for resection of intraspinal tumors. Relevant indicators between both groups of patients were compared, including length of surgical incision, duration of surgery, postoperative drainage volume, time to first out-of-bed activity after surgery, postoperative hospitalization period, visual analog score (VAS) score, and Japanese Orthopedic Association (JOA) score, at 1 month after surgery. RESULTS: Compared with the conventional laminectomy group, patients who underwent microsurgical resection with the aid of Caspar retractors had better outcomes in terms of length of surgical incision, postoperative drainage volume, time to first out-of-bed activity after surgery, postoperative hospitalization period, and VAS scores (p < 0.05). However, JOA scores at 1 month after surgery did not have any significant differences (p > 0.05). CONCLUSIONS: The microsurgical resection of intraspinal tumors with the aid of Caspar retractors has advantages of small trauma, less bleeding, and faster recovery. It is a safe and efficacious method for treating small intraspinal tumors.

Accuracy of magnetic resonance imaging texture analysis in differentiating low-grade from high-grade gliomas: systematic review and meta-analysis.

OBJECTIVES: Texture analysis (TA) is a method used for quantifying the spatial distributions of intensities in images using scanning software. MRI TA could be applied to grade gliomas. This meta-analysis was performed for assessing the accuracy of MRI TA in differentiating low-grade gliomas from high-grade ones. METHODS: PubMed, Cochrane Library, Science Direct and Embase were searched for identifying suitable studies from their inception to 1 September 2018. The quality of the studies was evaluated on the basis of the Quality Assessment of Diagnostic Accuracy Studies guidelines. We estimated the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic OR (DOR) using the summary receiver operating characteristic (SROC) for identifying the accuracy of MRI TA in grading gliomas. Fagan nomogram was applied for assessing the clinical utility of TA. RESULTS: Six studies including 440 patients were included and analysed. The pooled sensitivity, specificity, PLR, NLR and DOR with 95% CIs were 0.93 (95% CI 0.88 to 0.96), 0.86 (95% CI 0.81 to 0.89), 6.4 (95% CI 4.8 to 8.6), 0.08 (95% CI 0.05 to 0.15) and 78 (95% CI 39 to 156), respectively. The SROC curve showed an area under the curve of 0.96 (95% CI 0.93 to 0.97). Deeks test confirmed no significant publication bias in all studies. Fagan nomogram revealed that the post-test probability increased by 43% in patients with positive pre-test. CONCLUSIONS: The findings of this meta-analysis suggested that MRI TA has high accuracy in differentiating low-grade gliomas from high-grade ones. A standardised methodology is warranted to guide the use of this technique for clinical decision-making.

A hierarchical Nb2O5@NiFe-MMO rod array, fabricated and used as a structured photocatalyst.

Recently, using sunlight as a driving force with transitional metal oxides as photocatalysts, due to their unique optical and catalytic properties for organic reactions, has been considered to be a promising strategy in synthetic chemistry. Here, a hierarchically structured photocatalyst, a NiFe mixed metal oxide coated Nb2O5 (denoted as Nb2O5@NiFe-MMO) rod array has been successfully fabricated using Nb foil as a substrate. The Nb2O5 rod array was synthesized by the oxidative etching of Nb metal on the surface of the a substrate. The coating NiFe-MMO was obtained by the calcination of a NiFe layered double hydroxide (NiFe-LDH) precursor via the in situ epitaxial growing technique. The Nb2O5@NiFe-MMO rod array extended the photoresponse light region from ultraviolet light around 400 nm to visible light around 600 nm. With the well-designed architecture and highly dispersed NiO and Fe2O3, the as-prepared photocatalyst exhibited excellent activity and recyclability toward the reaction of aerobic coupling under relatively green conditions, with catalytic efficiency of 228 µmol cm-2 (the area is that of the Ni foil substrate) at 30 °C for 5 h. The present work provides a new strategy for the exploration of excellent structured photocatalysts based on transition metal oxide materials for selective aerobic oxidation of benzylamine to imine.

Inhibition of tumor growth and angiogenesis by 2-(4-aminophenyl) benzothiazole in orthotopicglioma C6 rat model.

In the present study antitumor effect of 2-(4-aminophenyl) benzothiazole (BTZ) was evaluated against human U251 and rat C6 glioma cell lines using MTT assay. It was observed that BTZ exhibited significant antitumor effect with IC50 of 3.5 and 4 µM against human U251 and rat C6 glioma cells respectively. To gain in-depth insights about the antitumor effect of BTZ, glioma xenograft rat model was prepared. The rats were treated with 10 mg and 15 mg/kg body weight doses of BTZ daily for 21 days after C6 cell administration. Treatment of the rats with BTZ reduced the tumor volume to 12% compared to 100% in the untreated rats. TUNEL assay showed a remarkable increase in the proportion of apoptotic cells in the BTZ treated rats than those in the untreated rats. The increase in the population of apoptotic cells was 23-fold compared to control. Immuno-histological staining revealed marked reduction (16%) in the proportion of CD31-stained vessels in the BTZ treated rats than those of the untreated rats. These changes were accompanied with decreased transcript levels of vascular endothelial growth factor (VEGF) and the VEGF receptor Flt1 as well as ERK1/2 and matrix metalloproteinase-2 (MMP2). Moreover, BTZ altered the expression of several cell cycle control proteins. While as pRb protein expression decreased, E2F1 remained unaltered and cyclin D1 protein and p53 expression was enhanced. Taken together, the results indicate that BTZ is a potent inhibitor of glioma cell proliferation in vivo and exerts its effects on cell cycle control and angiogenesis related proteins.

Galangin increases ERK1/2 phosphorylation to decrease ADAM9 expression and prevents invasion in A172 glioma cells.

Galangin (3,5,7­trihydroxyflavone), is a natural flavonoid present in plants. Galangin is reported to exhibit anti­cancer properties against various cancer types. The aim of the present study was to display the effects of galangin on glioma and its mechanism of action in A172 human glioma cancer cells. The results clearly indicated that treatment of galangin inhibited A172 cell migration and invasion under non­toxic doses. A human proteinase array assay was conducted to elucidate the potential effects of galangin, and the obtained results demonstrated that treatment of galangin inhibited ADAM9 protein expression and mRNA expression, that are known to contribute to cancer progression. Sustained extracellular signal­regulated kinase (Erk)1/2 activation was also monitored, which contributed to ADAM9 protein expression and mRNA inhibition as investigated using western blotting analysis and reverse transcription­quantitative polymerase chain reaction experiment. Erk1/2 inhibition by inhibitor or small interfering (si)Erk transfection markedly terminated galangin­inhibited A172 migration and invasion via an Erk1/2 activation mechanism. Collective results suggested that galangin may act as an effective chemotherapeutic agent for glioma cancer depending on its ability to bring about ADAM9 and Erk1/2 activation.

The risk of postoperative hemorrhage and efficacy of heparin for preventing deep vein thrombosis and pulmonary embolism in adult patients undergoing neurosurgery: a systematic review and meta-analysis.

The aim of this meta-analysis was to examine the risk of postoperative bleeding and efficacy of heparin for preventing deep vein thrombosis (DVT) and pulmonary embolism (PE) in adult patients undergoing neurosurgery. MEDLINE, Cochrane, and EMBASE databases were searched until October 31, 2016, for randomized controlled trials (RCTs) and non-randomized comparative studies that assessed the rates of postoperative hemorrhage, DVT, PE, and mortality in adult patients undergoing neurosurgery. Nine eligible studies (five RCTs, four retrospective studies) including 874 patients treated with either unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) and 1033 patients in control group (placebo with or without compression device) were analyzed. The overall analysis revealed that there was an increase in the risk of postoperative hemorrhage in patients who received heparin (pooled OR 1.66, 95% CI 1.01 to 2.72, p=0.046) compared with no treatment group. The risk of postoperative hemorrhage was more significant if only RCTs were included in analysis. Heparin prophylaxis was associated with a decrease in the risk of DVT (pooled OR 0.48, 95% CI 0.36 to 0.65, p<0.001) and PE (pooled OR 0.25, 95% CI 0.09 to 0.73, p=0.011) but it did not affect the rate of mortality. In conclusion, heparin increased the rate of postoperative bleeding, decreased the risk of DVT, PE and venous thromboembolic event (VTE) but it did not affect the mortality of patients undergoing neurosurgery. For the heparin prophylaxis, the trade-off between the risk of postoperative bleeding and benefit of prophylaxis against VTEs requires further investigation.

MiR-338-5p suppresses proliferation, migration, invasion, and promote apoptosis of glioblastoma cells by directly targeting EFEMP1.

OBJECTIVE: We aimed to investigate the effect of miR-338-5p on proliferation, migration and invasion of glioblastoma (GBM) cells by regulating EFEMP1. METHODS: The expression of miR-338-5p and EFEMP1 was measured by qRT-PCR and western blot. Transfection was conducted to regulate the expression of miR-338-5p and EFEMP1 in U87 cell lines. Cell proliferation, apoptosis, migration and invasion were evaluated using CCK-8 assay, flow cytometry and Transwell assay respectively. Dual luciferase reporter assay was performed to verify whether miR-338-5p directly targeted EFEMP1. RESULTS: MiR-338-5p was significantly down-regulated in human GBM tumor tissues and cells while EFEMP1 was strongly upregulated (P<0.05). Upregulated miR-338-5p was able to suppress cell proliferation, migration, invasion, and promote cell apoptosis in GBM cells (P<0.05). Dual luciferase reporter gene assay determined that miR-338-5p directly targeted EFEMP1 (P<0.05). CONCLUSIONS: MiR-338-5p suppressed proliferation, migration and invasion of GBM cells through inhibiting EFEMP1.

Conditioned media from human adipose tissue-derived mesenchymal stem cells and umbilical cord-derived mesenchymal stem cells efficiently induced the apoptosis and differentiation in human glioma cell lines in vitro.

Human mesenchymal stem cells (MSCs) have an intrinsic property for homing towards tumor sites and can be used as tumor-tropic vectors for tumor therapy. But very limited studies investigated the antitumor properties of MSCs themselves. In this study we investigated the antiglioma properties of two easily accessible MSCs, namely, human adipose tissue-derived mesenchymal stem cells (ASCs) and umbilical cord-derived mesenchymal stem cells (UC-MSCs). We found (1) MSC conditioned media can significantly inhibit the growth of human U251 glioma cell line; (2) MSC conditioned media can significantly induce apoptosis in human U251 cell line; (3) real-time PCR experiments showed significant upregulation of apoptotic genes of both caspase-3 and caspase-9 and significant downregulation of antiapoptotic genes such as survivin and XIAP after MSC conditioned media induction in U 251 cells; (4) furthermore, MSCs conditioned media culture induced rapid and complete differentiation in U251 cells. These results indicate MSCs can efficiently induce both apoptosis and differentiation in U251 human glioma cell line. Whereas UC-MSCs are more efficient for apoptosis induction than ASCs, their capability of differentiation induction is not distinguishable from each other. Our findings suggest MSCs themselves have favorable antitumor characteristics and should be further explored in future glioma therapy.

Co-transplantation of GDNF-overexpressing neural stem cells and fetal dopaminergic neurons mitigates motor symptoms in a rat model of Parkinson's disease.

Striatal transplantation of dopaminergic (DA) neurons or neural stem cells (NSCs) has been reported to improve the symptoms of Parkinson's disease (PD), but the low rate of cell survival, differentiation, and integration in the host brain limits the therapeutic efficacy. We investigated the therapeutic effects of intracranial co-transplantation of mesencephalic NSCs stably overexpressing human glial-derived neurotrophic factor (GDNF-mNSCs) together with fetal DA neurons in the 6-OHDA rat model of PD. Striatal injection of mNSCs labeled by the contrast enhancer superparamagnetic iron oxide (SPIO) resulted in a hypointense signal in the striatum on T2-weighted magnetic resonance images that lasted for at least 8 weeks post-injection, confirming the long-term survival of injected stem cells in vivo. Co-transplantation of GDNF-mNSCs with fetal DA neurons significantly reduced apomorphine-induced rotation, a behavioral endophenotype of PD, compared to sham-treated controls, rats injected with mNSCs expressing empty vector (control mNSCs) plus fetal DA neurons, or rats injected separately with either control mNSCs, GDNF-mNSCs, or fetal DA neurons. In addition, survival and differentiation of mNSCs into DA neurons was significantly greater following co-transplantation of GDNF-mNSCs plus fetal DA neurons compared to the other treatment groups as indicated by the greater number of cell expressing both the mNSCs lineage tracer enhanced green fluorescent protein (eGFP) and the DA neuron marker tyrosine hydroxylase. The success of cell-based therapies for PD may be greatly improved by co-transplantation of fetal DA neurons with mNSCs genetically modified to overexpress trophic factors such as GDNF that support differentiation into DA cells and their survival in vivo.

The maximum tolerated dose of gamma radiation to the optic nerve during γ knife radiosurgery in an animal study.

BACKGROUND: The safety of gamma knife radiosurgery should be considered when treating pituitary adenomas. OBJECTIVES: To determine the maximum tolerated dose of radiation delivered by gamma knife radiosurgery to optic nerves. METHODS: An animal model designed to establish prolonged balloon compression of the optic chiasm and parasellar region was developed to mimic the optic nerve compression caused by pituitary adenomas. Twenty cats underwent surgery to place a balloon for compression effect and 20 cats in a sham operation group received microsurgery without any treatment. The effects of gamma knife irradiation at 10-13 Gy on normal (sham operation group) and compressed (optic nerve compression group) optic nerves were investigated by pattern visual evoked potential examination and histopathology. RESULTS: Gamma knife radiosurgery at 10 Gy had almost no effect. At 11 Gy, P100 latency was significantly prolonged and P100 amplitude was significantly decreased in compressed optic nerves, but there was little change in the normal optic nerves. Doses of 11 Gy and higher induced significant electrophysiological variations and degeneration of the myelin sheath and axons in both normal and compressed optic nerves. CONCLUSIONS: Compressed optic nerves are more sensitive to gamma knife radiosurgery than normal optic nerves. The minimum dose of gamma knife radiosurgery that causes radiation injury in normal optic nerves is 12 Gy; however, the minimum dose is 11 Gy in compressed optic nerves.

Superparamagnetic iron oxide labeling of spinal cord neural stem cells genetically modified by nerve growth factor-beta.

This study established superparamagnetic iron oxide (SPIO)-labeled nerve growth factor-beta (NGF-beta) gene-modified spinal cord-derived neural stem cells (NSCs). The E14 rat embryonic spinal cord-derived NSCs were isolated and cultured. The cells of the third passage were transfected with plasmid pcDNA3-hNGFbeta by using FuGENE HD transfection reagent. The expression of NGF-beta was measured by immunocytochemistry and Western blotting. The positive clones were selected, allowed to proliferate and then labeled with SPIO, which was mediated by FuGENE HD transfection reagent. Prussian blue staining and transmission electron microscopy (TEM) were used to identify the SPIO particles in the cells. The distinctive markers for stem cells (nestin), neuron (beta-III-tubulin), oligodendrocyte (CNPase) and astrocyte (GFAP) were employed to evaluate the differentiation ability of the labeled cells. The immunocytochemistry and western blotting showed that NGF-beta was expressed in spinal cord-derived NSCs. Prussian blue staining indicated that numerous blue-stained particles appeared in the cytoplasma of the labeled cells. TEM showed that SPIO particles were found in vacuolar structures of different sizes and the cytoplasma. The immunocytochemistry demonstrated that the labeled cells were nestin-positive. After differentiation, the cells expressed beta-III-tubulin, CNPase and GFAP. It was concluded that the SPIO-labeled NGF-beta gene-modified spinal cord-derived NSC were successfully established, which are multipotent and capable of self-renewal.

Superparamagnetic Iron Oxide Labeling of Spinal Cord Neural Stem Cells Genetically Modified by Nerve Growth Factor-β / 华中科技大学学报（医学）（英德文版）

This study established superparamagnetic iron oxide (SPIO)-labeled nerve growth factor-β (NGF-β) gene-modified spinal cord-derived neural stem cells (NSCs).The E14 rat embryonic spinal cord-derived NSCs were isolated and cultured.The cells of the third passage were transfected with plasmid pcDNA3-hNGFβ by using FuGENE HD transfection reagent.The expression of NGF-β was measured by immunocytochemistry and Western blotting.The positive clones were selected,allowed to proliferate and then labeled with SPIO,which was mediated by FuGENE HD transfection reagent.Prussian blue staining and transmission electron microscopy (TEM) were used to identify the SPIO particles in the cells.The distinctive markers for stem cells (nestin),neuron (β-Ⅲ-tubulin),oligodendrocyte (CNPase) and astrocyte (GFAP) were employed to evaluate the differentiation ability of the labeled cells.The immunocytochemistry and western blotting showed that NGF-β was expressed in spinal cord-derived NSCs.Prussian blue staining indicated that numerous blue-stained particles appeared in the cytoplasma of the labeled cells.TEM showed that SPIO particles were found in vacuolar structures of different sizes and the cytoplasma.The immunocytochemistry demonstrated that the labeled cells were nestin-positive.After differentiation,the cells expressed β-Ⅲ-tubulin,CNPase and GFAE It was concluded that the SPIO-labeled NGF-β gene-modified spinal cord-derived NSC were successfully established,which are multipotent and capable of self-renewal.