Robot-Guided Stereotactic Puncture and Drainage in the Treatment of Thalamic Abscess.

Brain abscess is rare in clinic, the reported incidence is only 0.4 to 0.90 per 100,000 population, and most of them have a history of prodromal infection. Headache and fever are the most common clinical symptoms, and only a few are accompanied by neurological disorders. For the treatment of brain abscess, the most commonly used treatment is stereotactic puncture drainage and antibacterial therapy. A patient with a left thalamic abscess with no history of prodromal infection was reported. Stereotactic puncture and drainage were performed under the guidance of the Ruimi robot. The bacterial culture of the abscess was Streptococcus constellation ( Streptococcus constellatus ). The patient was discharged after 4 weeks of antibacterial treatment with vancomycin. The patients were followed up half a year after the operation, the prognosis was good and there was no recurrence.

Rectal chloral hydrate sedation for computed tomography in young children with head trauma.

ABSTRACT: Children evaluated in the emergency department for head trauma often undergo computed tomography (CT), with some uncooperative children requiring pharmacological sedation. Chloral hydrate (CH) is a sedative that has been widely used, but its rectal use for child sedation after head trauma has rarely been studied. The objective of this study was to document the safety and efficacy of rectal CH sedation for cranial CT in young children.We retrospectively studied all the children with head trauma who received rectal CH sedation for CT in the emergency department from 2016 to 2019. CH was administered rectally at a dose of 50 mg/kg body weight. When sedation was achieved, CT scanning was performed, and the children were monitored until recovery. The sedative safety and efficacy were analyzed.A total of 135 children were enrolled in the study group, and the mean age was 16.05 months. The mean onset time was 16.41 minutes. Successful sedation occurred in 97.0% of children. The mean recovery time was 71.59 minutes. All of the vital signs were within normal limits after sedation, except 1 (0.7%) with transient hypoxia. There was no drug-related vomiting reaction in the study group. Adverse effects occurred in 11 patients (8.1%), but all recovered completely. Compared with oral CH sedation, rectal CH sedation was associated with quicker onset (P < .01), higher success rate (P < .01), and lower adverse event rate (P < .01).Rectal CH sedation can be a safe and effective method for CT imaging of young children with head trauma in the emergency department.

Chordoid Glioma: A Neoplasm Found in the Anterior Part of the Third Ventricle.

ABSTRACT: Chordoid glioma is a rare low-grade tumor that originates almost exclusively in the anterior part of the third ventricle. The diagnosis and treatment of the tumor remain controversial. In this article, the authors present a novel case of chordoid glioma of the third ventricle. The patient was treated with less invasive microsurgery followed by low-dose gamma knife radiosurgery. Magnetic resonance imaging revealed a decrease in tumor size and necrosis in the central region of the tumor, without significant complications at follow-up 14 months later. Based on these findings, the authors suggest that less invasive microsurgical resection followed by low-dose gamma knife radiosurgery is safe and effective for the treatment of chordoid glioma of the third ventricle.

Efficacy and safety profile of neuroendoscopic hematoma evacuation combined with intraventricular lavage in severe intraventricular hemorrhage patients.

OBJECTIVE: The present study was conducted to explore the effect of neuroendoscopic hematoma evacuation in severe intraventricular hemorrhage (IVH). METHODS: Totally 81 patients with severe IVH in our hospital from November 2017 to March 2019 were divided into the intervention group (38 cases who received neuroendoscopic hematoma evacuation combined with intraventricular lavage) and the control group (40 cases who received trepanation drainage). The perioperative condition, hematoma clearance rate, Glasgow coma score (GCS), hematoma recurrence rate, and prognosis were observed and compared between the two groups after treatment. RESULTS: The operative time, time of cerebrospinal fluid drainage, and intracranial infection rate in the intervention group elicited superior results to those in the control group (p < .05). The clearance rate of hematoma in the intervention group was higher than that in the control group at 6 hr, 1, 3, and 7 days postoperatively (p < .05). The postoperative 3- and 7-day GCS scores in the intervention group were higher than those in the control group, and the recurrence rate of hematoma in the intervention group was significantly lower than that in the control group (p < .05), and the good/excellent rate of ADL in the intervention group was significantly higher than that in the control group (p < .05). CONCLUSION: Neuroendoscopic hematoma evacuation combined with intraventricular lavage showed evident beneficial outcomes in patients with severe IVH. It can effectively improve the perioperative condition and improve the hematoma clearance rate and is beneficial to the prognosis of patients with severe IVH.

Role of Asparagine Endopeptidase in Mediating Wild-Type p53 Inactivation of Glioblastoma.

BACKGROUND: Isocitrate dehydrogenase wild-type (WT) glioblastoma (GBM) accounts for 90% of all GBMs, yet only 27% of isocitrate dehydrogenase WT-GBMs have p53 mutations. However, the tumor surveillance function of WT-p53 in GBM is subverted by mechanisms that are not fully understood. METHODS: We investigated the proteolytic inactivation of WT-p53 by asparaginyl endopeptidase (AEP) and its effects on GBM progression in cancer cells, murine models, and patients' specimens using biochemical and functional assays. The sera of healthy donors (n = 48) and GBM patients (n = 20) were examined by enzyme-linked immunosorbent assay. Furthermore, effects of AEP inhibitors on GBM progression were evaluated in murine models (n = 6-8 per group). The statistical significance between groups was determined using two-tailed Student t tests. RESULTS: We demonstrate that AEP binds to and directly cleaves WT-p53, resulting in the inhibition of WT-p53-mediated tumor suppressor function in both tumor cells and stromal cells via extracellular vesicle communication. High expression of uncleavable p53-N311A-mutant rescue AEP-induced tumorigenesis, proliferation, and anti-apoptotic abilities. Knock down or pharmacological inhibition of AEP reduced tumorigenesis and prolonged survival in murine models. However, overexpression of AEP promoted tumorigenesis and shortened the survival time. Moreover, high AEP levels in GBM tissues were associated with a poor prognosis of GBM patients (n = 83; hazard ratio = 3.94, 95% confidence interval = 1.87 to 8.28; P < .001). A correlation was found between high plasma AEP levels and a larger tumor size in GBM patients (r = 0.6, P = .03), which decreased dramatically after surgery. CONCLUSIONS: Our results indicate that AEP promotes GBM progression via inactivation of WT-p53 and may serve as a prognostic and therapeutic target for GBM.

Difference in the Inhibitory Effect of Temozolomide on TJ905 Glioma Cells and Stem Cells.

This study aims to determine the difference in the inhibitory effect of temozolomide (TMZ) on TJ905 glioma cells and stem cells. TJ905 cancer stem cells were isolated. Livin is a member of the inhibitor of apoptosis protein family. The TJ905 cells and cancer stem cells were transfected with a Livin-shRNA and negative-shRNA, respectively, and then treated with TMZ. At 48 h post-transfection, a cell counting kit 8 assay, flow cytometry, and real-time qPCR were performed to detect cell proliferation, the cell cycle, and the expression of the Caspase-3, -7, and -9 mRNAs, respectively. As a result, the suppressive effect of TMZ on TJ905 cells was more significant than its effect on TJ905 cancer stem cells. TMZ exerted an inhibitory effect on the growth of TJ905 glioma cells by arresting them at G0/G1 phase and arresting cancer stem cells at S phase in a dose-dependent manner. TMZ inhibited Livin mRNA expression and increased the expression of the Caspase-3, -7, and -9 mRNAs. Low Livin mRNA expression induced high levels of Caspase-3, -7, and -9 expressions, thus promoting the apoptosis of both TJ905 cells and cancer stem cells in response to TMZ treatment. The TJ905 cells transfected with the Livin-shRNA were more sensitive to TMZ, whereas the TJ905 glioma stem cells transfected with the Livin-shRNA showed no significant changes in their sensitivity to TMZ. In conclusion, the Livin gene may play an important role in the resistance mechanisms of TJ905 glioma cells and cancer stem cells. However, Livin had a more distinct role in TMZ resistance, cell proliferation, and the cell cycle in TJ905 glioma cells than in cancer stem cells.

Overexpression of FoxO3a is associated with glioblastoma progression and predicts poor patient prognosis.

Forkhead transcription factor FoxO3a has been reported to have ambiguous functions and distinct mechanisms in various solid tumors, including glioblastoma (GBM). Although a preliminary analysis of a small sample of patients indicated that FoxO3a aberrations in glioma might be related to aggressive clinical behavior, the clinical significance of FoxO3a in glioblastoma remains unclear. We investigated the expression of FoxO3a in a cohort of 91 glioblastoma specimens and analyzed the correlations of protein expression with patient prognosis. Furthermore, the functional impact of FoxO3a on GBM progression and the underlying mechanisms of FoxO3a regulation were explored in a series of in vitro and in vivo assays. FoxO3a expression was elevated in glioblastoma tissues, and high nuclear FoxO3a expression in human GBM tissues was associated with poor prognosis. Moreover, knockdown of FoxO3a significantly reduced the colony formation and invasion ability of GBM cells, whereas overexpression of FoxO3a promoted the colony formation and invasion ability. The results of in vivo GBM models further confirmed that FoxO3a knockdown inhibited GBM progression. More, the pro-oncogenic effects of FoxO3a in GBM were mediated by the activation of c-Myc, microtubule-associated protein 1 light chain 3 beta (LC3B) and Beclin1 in a mixed-lineage leukemia 2 (MLL2)-dependent manner. These findings suggest that high FoxO3a expression is associated with glioblastoma progression and that FoxO3a independently indicates poor prognosis in patients. FoxO3a might be a novel prognostic biomarker or a potential therapeutic target in glioblastoma.

Effect of Corilagin on the Proliferation and NF-κB in U251 Glioblastoma Cells and U251 Glioblastoma Stem-Like Cells.

Background. This study is to explore the effect of corilagin on the proliferation and NF-κB signaling pathway in U251 glioblastoma cells and U251 glioblastoma stem-like cells. Methods. CD133 positive U251 glioblastoma cells were separated by immunomagnetic beads to isolate glioblastoma stem-like cells. U251 cells and stem-like cells were intervened by different corilagin concentrations (0, 25, 50, and 100 µg/mL) for 48 h, respectively. Cell morphology, cell counting kit-8 assay, flow cytometry, dual luciferase reporter assay, and a western blot were used to detect and analyze the cell proliferation and cell cycle and investigate the expression of IKBα protein in cytoplasm and NF-κB/p65 in nucleus. Results. Corilagin inhibited the cell proliferation of U251 cells and their stem-like cells and the inhibition role was stronger in U251 stem-like cells (P < 0.05). The cell cycle was arrested at G2/M phase in the U251 cells following corilagin intervention; the proportion of cells in G2/M phase increased as the concentration of corilagin increased (P < 0.05). The U251 stem-like cells were arrested at the S phase following treatment with corilagin; the proportion of cells in the S phase increased as the concentration of corilagin increased (P < 0.05). The ratio of dual luciferase activities of U251 stem-like cells was lower than that of U251 cells in the same corilagin concentration. With increasing concentrations of corilagin, the IKBα expression in cytoplasm of U251 cells and U251 stem-like cells was increased, but the p65 expression in nucleus of U251 cells and U251 stem-like cells was decreased (P < 0.05). Conclusion. Corilagin can inhibit the proliferation of glioblastoma cells and glioblastoma stem-like cells; the inhibition on glioblastoma stem-like cell proliferation is stronger than glioblastoma cells. This different result indicates that the effect of corilagin on U251 cells and U251 stem-like cells may have close relationships with mechanism of cell cycle and NF-κB signaling pathway; however, the real antitumor mechanism of corilagin is not yet clear and requires further study.

Feasibility of three-dimensional ultrashort echo time magnetic resonance imaging at 1.5 T for the diagnosis of skull fractures.

OBJECTIVES: To investigate the feasibility of ultrashort echo time (UTE) magnetic resonance imaging (MRI) for the diagnosis of skull fractures. METHODS: The skull fracture models of ten Bama pigs and 364 patients with craniocerebral trauma were subjected to computed tomography (CT), UTE and conventional MRI sequences. The accuracy of UTE imaging in skull fracture diagnosis was analysed using receiver operating characteristic (ROC) curve analysis, McNemar's test and Kappa values. Differences among CT, UTE imaging and anatomical measurement (AM) values for linear fractures (LFs) and depressed fractures (DFs) were compared using one-way ANOVA and a paired-samples t-test. RESULTS: UTE imaging clearly demonstrated skull structures and fractures. The accuracy, validity and reliability of UTE MRI were excellent, with no significant differences between expert readings (P > 0.05; Kappa, 0.899). The values obtained for 42 LFs and 13 DFs in the ten specimens were not significantly different among CT, UTE MRI and AMs, while those obtained for 55 LFs and ten DFs in 44 patients were not significantly different between CT and UTE MRI (P > 0.05). CONCLUSIONS: UTE MRI sequences are feasible for the evaluation of skull structures and fractures, with no radiation exposure, particularly for paediatric and pregnant patients. KEY POINTS: Despite ionising radiation, CT is standard for skull fracture assessment. Conventional MRI cannot depict skull structures. 3D-UTE sequences clearly demonstrate skull structures and fractures. UTE plus conventional MRI are superior to CT in craniocerebral trauma assessment. Paediatric and pregnant patients will benefit from this imaging modality.

IDH1R¹³²H decreases the proliferation of U87 glioma cells through upregulation of microRNA-128a.

Mutations in isocitrate dehydrogenase 1 (IDH1) are found in >70% of secondary glioblastomas and lower-grade gliomas (grades II-III). Among the numerous phenotypic differences between IDH1 mutant and wild-type glioma patients, the most salient is an improved survival rate for patients with a mutation. MicroRNAs (miRNAs) are a class of small, non­coding, single­stranded RNAs that can negatively regulate gene expression at the post­transcriptional level, predominantly by binding to the 3'­untranslated region of their target mRNAs. The dysregulated expression of several miRNAs has been reported to modulate glioma progression; however, it is unclear whether mutations in IDH1 regulate glioma cell proliferation through miRNA dysregulation. In the present study, stable overexpression of IDH1WT or IDH1R132H was established in the U87 glioma cell line. It was found that IDH1R132H decreased cell proliferation of U87 glioma cells by inducing the expression of the miRNA miR­128a. This process was dependent on the transcription factor hypoxia inducible factor­1α (HIF­1α), which binds to a hypoxia response element in the promoter of miR­128a. Furthermore, miR­128a negatively regulated the expression of B­cell­specific Moloney murine leukemia virus integration site 1 protein (Bmi­1), which is involved in suppressing cell proliferation. These findings suggest that the IDH1R132H­HIF­1α­miR­128a­Bmi­1 pathway is involved in glioma cell proliferation.

Silencing of Id2 attenuates hypoxia/ischemia-induced neuronal injury via inhibition of neuronal apoptosis.

Cerebral ischemic stroke has long been recognized as a prevalent and serious neurological disease that was associated with high mortality and morbidity. However, the current therapeutic protocols remain suboptimal with major mechanisms underlying stroke urgently warranted. Inhibitor of DNA binding/differentiation 2 (Id2) is found to be up-regulated in neuronal cells following hypoxia/ischemia (H/I). This study was aimed to investigate whether knockdown of Id2 in neuronal cells could protect them from hypoxic and ischemic injury both in vitro and in vivo. Flow cytometric analysis was employed to assess neuronal apoptosis in CoCl2-treated neuroblastoma B35 cells engineered to overexpress or knockdown Id2 expression. In vivo knockdown of Id2 was performed in Sprague-Dawley rats by a single intracerebroventricular injection of Cy3-labeled and cholesterol-modified Id2-siRNA. We found that knockdown of Id2 attenuated H/I-induced neuronal apoptosis in vitro while overexpression of Id2 produced an opposite effect. In a rat model of middle cerebral artery occlusion (MCAO), in vivo knockdown of Id2 significantly improved neurological deficits, reduced the volume of ischemic infarction and diminished the neuronal apoptosis in the penumbra area. Double immunofluorescence staining showed less co-localization of retinoblastoma tumor suppressor protein (Rb)-Id2 but greater co-localization of Rb-E2F1 in the penumbra area. Cell cycle assay further demonstrated that Id2 knockdown induced G0/G1 cell cycle arrest in CoCl2-treated B35 cells. The present data support the implication of Id2 in the modulation of H/I-induced neuronal apoptosis and may provide a potential therapeutic option to protect brain tissues from ischemic injury by inhibition of its expression.

Early-stage hemangioblastoma presenting as a small lesion with significant edema in the cerebellum.

Hemangioblastomas are benign tumors that are frequently associated with peritumoral cysts; however, their early characteristics before cyst formation remain unclear. In this article, the authors present a novel case of a cerebellar hemangioblastoma presenting as a small solid lesion with significant edema. Surgery was performed to resect the tumor, and a follow-up magnetic resonance imaging scan revealed complete excision of the mass and resolution of the cerebellar edema. Histological examination confirmed that the lesion was a hemangioblastoma. This is the only report in the literature to describe the imaging and histopathologic characteristics of an initial hemangioblastoma in the cerebellum.

Overexpression of isocitrate dehydrogenase-1R¹³²H enhances the proliferation of A172 glioma cells via aerobic glycolysis.

Gliomas are the most common type of primary malignancy of the central nervous system. The identification of mutations in the gene encoding isocitrate dehydrogenase­1 (IDH1) represents a key area of investigation in studies on glioma. The IDH1R132H mutation is a heterozygous point mutation, which affects the amino acid arginine at position 132, however, the metabolic importance of this mutation in tumor cell growth remains to be elucidated. In the present study, A172 glioma cell lines stably overexpressing either wild­type IDH1 or IDH1R132H were produced. The results demonstrated that the IDH1R132H mutation enhanced the proliferation of the A172 glioma cells in vitro. Furthermore, IDH1R132H performed this function by elevating the expression levels of hypoxia inducible factor­1α, leading to an increase in the expression levels of the key glycolytic enzymes, glucose transporter 1 and hexokinase 2. Therefore, the metabolism was shifted towards aerobic glycolysis, leading to an increase in glucose uptake and lactate production. These findings demonstrated that the IDH1R132H molecular target was involved in orchestrating the Warburg effect in mutant IDH1R132H glioma cells.

Cerebral venous sinus thrombosis with cerebral hemorrhage during early pregnancy.

Cerebral venous sinus thrombosis (CVST) rarely induces cerebral hemorrhage, and CVST with cerebral hemorrhage during early pregnancy is extremely rare. Upon literature review, we are able to find only one case of CVST with cerebral hemorrhage in early pregnancy. In this paper, we report another case of a 27-year-old patient who developed CVST with cerebral hemorrhage in her fifth week of pregnancy. Although the optimal treatment for this infrequent condition remains controversial, we adopted anticoagulation as the first choice of treatment and obtained favorable results.

MiR-26a enhances the radiosensitivity of glioblastoma multiforme cells through targeting of ataxia-telangiectasia mutated.

Glioblastoma multiforme (GBM) is notoriously resistant to radiation, and consequently, new radiosensitizers are urgently needed. MicroRNAs are a class of endogenous gene modulators with emerging roles in DNA repair. We found that overexpression of miR-26a can enhance radiosensitivity and reduce the DNA repair ability of U87 cells. However, knockdown miR-26a in U87 cells could act the converse manner. Mechanistically, this effect is mediated by direct targeting of miR-26a to the 3'UTR of ATM, which leads to reduced ATM levels and consequent inhibition of the homologous recombination repair pathway. These results suggest that miR-26a may act as a new radiosensitizer of GBM.

C-Myc negatively controls the tumor suppressor PTEN by upregulating miR-26a in glioblastoma multiforme cells.

The c-Myc oncogene is amplified in many tumor types. It is an important regulator of cell proliferation and has been linked to altered miRNA expression, suggesting that c-Myc-regulated miRNAs might contribute to tumor progression. Although miR-26a has been reported to be upregulated in glioblastoma multiforme (GBM), the mechanism has not been established. We have shown that ectopic expression of miR-26a influenced cell proliferation by targeting PTEN, a tumor suppressor gene that is inactivated in many common malignancies, including GBM. Our findings suggest that c-Myc modulates genes associated with oncogenesis in GBM through deregulation of miRNAs via the c-Myc-miR-26a-PTEN signaling pathway. This may be of clinical relevance.

Hypoxia/ischemia up-regulates Id2 expression in neuronal cells in vivo and in vitro.

Inhibitor of DNA binding/differentiation 2 (Id2) belongs to a family of transcriptional modulators characterized by a helix-loop-helix (HLH) motif that lacks the basic amino acid domain necessary to bind DNA. The aim of this study was to obtain a better understanding of the role of Id2 in hypoxia/ischemia (H/I)-induced neuronal apoptosis. Following H/I induction in a rat model of middle cerebral artery occlusion (MCAO)/reperfusion, the number of TUNEL-positive cells in cerebral cortices of the penumbra area increased gradually, while the Id2 mRNA and protein expression were also significantly up-regulated. The hypoxia-mimetic, cobalt chloride (CoCl2)-treated rat neuroblastoma B35 cell line also demonstrated enhanced Id2 mRNA and protein expression as well as increased number of cells in the sub-G1 populations after H/I exposure. Consistently, the expression of Bax, a proapoptotic protein, was also up-regulated in vivo and in vitro. Moreover, triple immunofluorescence demonstrated the obvious co-localization of Id2, TUNEL and NeuN in neurons of the penumbra area. These data suggest that H/I up-regulates Id2 expression in neuronal cells, and Id2 might play an important role in H/I-induced neuronal apoptosis.

miR-708 acts as a tumor suppressor in human glioblastoma cells.

Glioblastoma (GBM) is one of the most lethal forms of human cancer, and new clinical biomarkers and therapeutic targets are urgently required. microRNAs (miRNAs) are small, non-coding RNAs that negatively regulate gene expression at the post-transcriptional and/or translational level by binding the 3' untranslated regions (3' UTRs) of target mRNAs. The dysregulated expression of several miRNAs has been reported to modulate glioma progression. In the present study, we defined the expression and function of miR-708, which, based on real-time PCR analysis, were downregulated in GBM cells. The overexpression of miR-708 inhibited cell proliferation and invasion and induced apoptosis in the human GBM cell lines A172 and T98G. Furthermore, the overexpression of miR-708 reduced the expression of Akt1, CCND1, MMP2, EZH2, Parp-1 and Bcl2 in A172 and T98G cells. Taken together, our study suggests that miR-708 affects GBM cell proliferation and invasion, and induces apoptosis. It is suggested that miR-708 may play an important role as a tumor suppressor in GBM and it may be an attractive target for therapeutic intervention in GBM.