Molecular diagnosis and treatment of meningiomas: an expert consensus (2022).

ABSTRACT: Meningiomas are the most common primary intracranial neoplasm with diverse pathological types and complicated clinical manifestations. The fifth edition of the WHO Classification of Tumors of the Central Nervous System (WHO CNS5), published in 2021, introduces major changes that advance the role of molecular diagnostics in meningiomas. To follow the revision of WHO CNS5, this expert consensus statement was formed jointly by the Group of Neuro-Oncology, Society of Neurosurgery, Chinese Medical Association together with neuropathologists and evidence-based experts. The consensus provides reference points to integrate key biomarkers into stratification and clinical decision making for meningioma patients. REGISTRATION: Practice guideline REgistration for transPAREncy (PREPARE), IPGRP-2022CN234.

Activation of Sigma-1 Receptor Alleviates ER-Associated Cell Death and Microglia Activation in Traumatically Injured Mice.

BACKGROUND: Endoplasmic reticulum (ER) stress and unfolded protein response (UPR) is associated with neuroinflammation and subsequent cell death following traumatic brain injury (TBI). The sigma-1 receptor (Sig-1R) acts as a dynamic pluripotent modulator of fundamental cellular processes at the mitochondria-associated membranes (MAMs). The activation of Sig-1R is neuroprotective in a variety of central nervous system diseases, but its impact on ER stress induced by traumatic brain injury is not known. This study investigated the role of Sig-1R in regulating the ER stress-mediated microglial activation and programmed cell death (apoptosis and pyroptosis) induced by TBI. METHODS: Ten human brain tissues were obtained from The Tianjin Medical University General Hospital. Four normal brain tissues were obtained from patients who underwent surgery for cerebral vascular malformation, through which peripheral brain tissues were isolated. Six severe TBI tissues were from patients with brain injury caused by accidents. None of the patients had any other known neurological disorders. Mice with Sig-1R deletion using CRISPR technology were subjected to controlled cortical impact-induced injury. In parallel, wild type C57BL/6J mice were analyzed for outcomes after they were exposed to TBI and received the Sig-1R agonist PRE-084 (10 mg/kg daily for three days) either alone or in combination with the Sig-1R antagonist BD-1047 (10 mg/kg). RESULTS: The expression of Sig-1R and the 78 kDa glucose-regulated protein, a known UPR marker, were significantly elevated in the injured cerebral tissues from TBI patients and mice subjected to TBI. PRE-084 improved neurological function, restored the cerebral cortical perfusion, and ameliorated and brain edema in C57BL/6J mice subjected to TBI by reducing endoplasmic reticulum stress-mediated apoptosis, pyroptosis, and microglia activation. The effect of PRE-084 was abolished in mice receiving Sig-1R antagonist BD-1047. CONCLUSIONS: ER stress and UPR were upregulated in TBI patients and mice subjected to TBI. Sig-1R activation by the exogenous activator PRE-084 attenuated microglial cells activation, reduced ER stress-associated programmed cell death, and restored cerebrovascular and neurological function in TBI mice.

Soft Coagulation Monopolar Suction for Rapid Resection of Supratentorial Brain Tumors: Feasibility of a New Technique and Outcomes.

OBJECTIVES: The aims of this study were to evaluate the feasibility of a new rapid tumor resection technique using soft coagulation monopolar suction (SCMS) and to strengthen neurosurgeons' understanding, use, and attention to this new electrosurgical technique. METHODS: The rapid surgical resection technique used herein comprised monopolar suction in soft coagulation mode applied by the ERBE VIO 300s workstation and conventional microsurgical suction. We applied this technique to supratentorial tumors in 12 patients (5 with glioblastomas, 4 with astrocytomas, 2 with metastases, and one with lymphoma) as the SCMS group. The conventional bipolar electrocautery and suction method was used for another 12 patients (non-SCMS group). The surgical results and perioperative complications were retrospectively evaluated. Radiographic and histologic analyses were performed to describe the degree of thermal damage. RESULTS: The mean estimated operative time and total blood loss were 3.63 ± 0.61 hours (P = 0.0048) and 308.33 ± 172.99 mL (P = 0.0482) in the SCMS group, respectively, and these values were significantly lower than those in the non-SCMS group (4.33 ± 0.49 hours and 466.67 ± 196.95 mL, respectively). No significant differences in perioperative complications, Karnofsky Performance Status scores, perioperative area edema volumes, perioperative ischemic areas, or mean residual tumors were observed between the groups. Histological examination revealed that SCMS produced uniform coagulation and completely obstructed most small vessel structures on the tumor surface. CONCLUSIONS: This new technique involving SCMS allows for a smooth surgical procedure and appears to be safe and feasible for the rapid resection of supratentorial brain tumors. Thus, neurosurgeons should consider using this technique in the future.

Risk Factor Analysis of the Conservative Treatment in Chronic Subdural Hematomas: A Substudy of the ATOCH Trial.

INTRODUCTION: The objective of the study was to analyze the risk factors for worsening of the disease progression in patients with chronic subdural hematomas (CSDH) during wait-and-observation treatment regimen and conservative treatment with atorvastatin. METHODS: A total of 196 patients with CSDH were recruited (98 in the atorvastatin group and 98 in the blank placebo group). Receiver operating characteristic (ROC) curve analysis was used to identify the optimal cutoff for the hematoma volume by testing surgical and nonsurgical outcomes. Other measures, including univariate and multivariate analyses, were performed to identify the potential significant factors indicative of the outcome of therapeutic efficacy of conservative treatment through the characteristics of the baseline indicators at enrollment. RESULTS: Over a median treatment duration of 2 months, lower total cholesterol, higher hematoma volume, and more midline shift were independent risk factors for worse outcomes of atorvastatin treatment for CSDH, and only a higher hematoma volume was an independent risk factor for spontaneous absorption in the placebo group. ROC analysis of all of the data showed that the optimal threshold of hematoma volume was 68.5 ml (sensitivity 73.5%, specificity 74%) in response to the greatest chance of switching to surgery. CONCLUSIONS: Critical independent predictors of atorvastatin monotherapy treatment success included higher total cholesterol, lower hematoma volume, and less midline shift in atorvastatin monotherapy, and higher hematoma volume was the only independent risk factor in close follow-up observation patients without any pharmacotherapy. Initial hematoma volume more than 68.5 ml may help clinicians to determine individual risk assessments and to make optimal treatment decisions. TRIAL REGISTRATION: http://www. CLINICALTRIALS: gov . Identifier NCT02024373.

Sigma-1 Receptor: A Potential Therapeutic Target for Traumatic Brain Injury.

The sigma-1 receptor (Sig-1R) is a chaperone receptor that primarily resides at the mitochondria-associated endoplasmic reticulum (ER) membrane (MAM) and acts as a dynamic pluripotent modulator regulating cellular pathophysiological processes. Multiple pharmacological studies have confirmed the beneficial effects of Sig-1R activation on cellular calcium homeostasis, excitotoxicity modulation, reactive oxygen species (ROS) clearance, and the structural and functional stability of the ER, mitochondria, and MAM. The Sig-1R is expressed broadly in cells of the central nervous system (CNS) and has been reported to be involved in various neurological disorders. Traumatic brain injury (TBI)-induced secondary injury involves complex and interrelated pathophysiological processes such as cellular apoptosis, glutamate excitotoxicity, inflammatory responses, endoplasmic reticulum stress, oxidative stress, and mitochondrial dysfunction. Thus, given the pluripotent modulation of the Sig-1R in diverse neurological disorders, we hypothesized that the Sig-1R may affect a series of pathophysiology after TBI. This review summarizes the current knowledge of the Sig-1R, its mechanistic role in various pathophysiological processes of multiple CNS diseases, and its potential therapeutic role in TBI.

Using a New Landmark of the Most External Point in the Embolization of Distal Anterior Choroidal Aneurysms: A Report of Two Cases.

There are landmarks on the course of the anterior choroidal artery (AChoA), such as the original point (OP) and the plexal point (PP), as documented in previous articles. In these previous articles, the AChoA was the terminal branch of the internal carotid artery (ICA), which had two segments throughout its course. The first cisternal segment began from the origin and ended at the point where the artery reached the choroidal fissure (the PP). The second segment consisted of one or more branches, which passed through the choroidal fissure and entered the choroid plexus. However, we found another angiographic landmark, named the most external point (MEP), along the course of the AChoA in the anteroposterior (AP) view. There was a sharp turn at the outermost limit of the course of the AChoA, and then the AChoA progressed inward and upward. We defined the outermost limit as the MEP of the AChoA. This study describes two rare cases of distal AChoA aneurysms associated with arteriovenous malformation (AVM) and Moyamoya disease that developed intraventricular hemorrhage, and we used the parent artery occlusion (PAO) technique to embolize the distal AChoA lesions at the MEP. The patients recovered well without any neurological complications.

Mouse nerve growth factor promotes neurological recovery in patients with acute intracerebral hemorrhage: A proof-of-concept study.

BACKGROUND: ew drugs were confirmed to be effective in the treatments of neurological dysfunction caused by acute intracerebral hemorrhage (ICH). The present prospective clinical trial aims to evaluate the effect of mouse nerve growth factor (mNGF) on neurological function in patients with acute ICH. METHODS: 60 patients with acute spontaneous ICH were randomized to receive mNGF (mNGF group) and citicoline (control group) for 4 weeks within 24-72 h after onset, respectively. The primary outcome was difference in the neurological functional outcome at 3 months by the modified Rankin Scale score (mRS). The secondary outcomes were the changes in hematoma volume at 4 weeks and 3 months. RESULTS: There were 55 patients receiving treatment (29 patients in the mNGF group, 26 patients in the control group). Among the patients, 46 patients finished the trial at 3 months; the odds of a shift towards death or dependence (mRS > 3) at 3 months in the mNGF group were lower than that in the control group with adjustment for age, sex, NIHSS at admission, and hematoma volume at admission (adjusted OR, 0.185; 95%CI, 0.059-0.582; P = 0.0039). The hematoma was gradually reduced in all 46 patients and absorbed after non-surgical treatment at 3 months. There was no significant difference in hematoma volume between the two groups. No serious adverse event was found. CONCLUSIONS: The administration of mNGF and citicoline was well-tolerated in patients with acute ICH. mNGF was associated with improved neurological function and less disability in patients with ICH. Therefore, the quality of life of patients with ICH may be improved by mNGF. TRIAL REGISTRATION: The trial is registered with the Chinese Clinical Trial Registry, number ChiCTR1800020258.

Use of a compact high-definition two-dimensional exoscope in surgical treatment of large vestibular schwannoma.

BACKGROUND: Extra-corporeal video telescope operating monitor system provides a necessary instrument to perform high-precision neurosurgical procedures that could substitute or supplement the traditional surgical microscope. The present study was designed to evaluate a compact high-definition two-dimensional exoscope system for assisting in surgical removal of large vestibular schwannoma (VS), as an alternative to a binocular surgical microscope. METHODS: Patients with Koos grade 3 and grade 4 VS undergoing surgery were enrolled in this prospective cohort study between January 2013 and June 2018. The demographics and tumor characteristics (size, Koos grade, composition [cystic or solid mass]) were matched between the two groups of patients. The following outcome measurements were compared between the two groups: duration of surgery, volume of blood loss, extent of tumor resection, number of operating field adjustments, pre- and post-operative facial and cochlear nerve function evaluated at 3 months post-surgery, complications and surgeons' comfortability. RESULTS: A total of 81 patients received tumor resection through the retrosigmoid approach under either an exoscope (cases, n = 39) or a surgical microscope (control, n = 42). Patients in the two groups had comparable tumor location (P = 0.439), Koos grading (P = 0.867), and composition (P = 0.891). While no significant differences in the duration of surgery (P = 0.172), extent of tumor resection (P = 0.858), facial function (P = 0.838), and hearing ability (P = 1.000), patients operated on under an exoscope had less blood loss (P = 0.036) and a fewer field adjustments (P < 0.001). Both primary and assistant surgeons reported a high level of comfort operating under the exoscope (P = 0.001 and P < 0.001, respectively). CONCLUSIONS: The compact high-definition two-dimensional exoscope system provides a safe and efficient means to assist in removing large VSs, as compared to a surgical microscope. After the acquaintance with a visual perception through a dynamic hint and stereoscopically viewing corresponding to the motion parallax, the exoscope system provided a comfortable, high-resolution visualization without compromising operational efficiency and patient safety.

Treatment of chronic subdural hematoma with atorvastatin combined with low-dose dexamethasone: phase II randomized proof-of-concept clinical trial.

OBJECTIVE: The authors sought to test the hypothesis that adding dexamethasone (DXM) to atorvastatin (ATO) potentiates the effects of ATO on chronic subdural hematoma (CSDH). METHODS: Sixty patients with CSDH underwent 5 weeks of treatment with an additional 7-week follow-up. Patients were randomized to receive a 5-week regimen of ATO 20 mg daily or ATO 20 mg daily plus a DXM regimen (ATO+DXM). The 5-week DXM regimen was 2.25 mg daily for 2 consecutive weeks, followed by 0.75 mg twice daily for 2 weeks and 0.75 mg once daily for 1 week. The primary endpoint was hematoma reduction assessed by neuroimaging at baseline and at 5 weeks of follow-up. Secondary outcomes included neurological improvement assessed by using the Markwalder's Grading Scale and Glasgow Coma Scale (MGS-GCS). RESULTS: The mean patient age was 66.6 years, and 25% of patients were women. The patients who were treated with ATO+DXM had more obvious hematoma reduction at the 5th week (between-groups difference 18.37 ml; 95% CI 8.17-28.57; p = 0.0005). This reduction started from the 2nd week (14.51 ml; 95% CI 4.31-24.71; p = 0.0056) of treatment and persisted until the 12th week (17.50 ml; 95% CI 7.30-27.70; p = 0.0009). Complete recovery of neurological function (MGS-GCS grade 0) at 5 weeks was achieved in 83.33% and 32.14% of patients in the ATO+DXM and ATO groups, respectively. At the 5th week, patients receiving ATO+DXM had significantly lower levels of T cells and higher levels of regulatory T cells and endothelial progenitor cells in their peripheral blood. CONCLUSIONS: ATO+DXM was more effective than ATO alone in reducing hematoma and improving neurological function in patients with CSDH. These results require further confirmation in a randomized placebo-controlled trial.Clinical trial registration no.: ChiCTR-IPR-14005573 (http://www.chictr.org.cn/index.aspx).

Risk factors for corticosteroid insufficiency during the sub-acute phase of acute traumatic brain injury.

Hypothalamic-pituitary-adrenal axis dysfunction may lead to the occurrence of critical illness-related corticosteroid insufficiency. Critical illness-related corticosteroid insufficiency can easily occur after traumatic brain injury, but few studies have examined this occurrence. A multicenter, prospective, cohort study was performed to evaluate the function of the hypothalamic-pituitary-adrenal axis and the incidence of critical illness-related corticosteroid insufficiency during the sub-acute phase of traumatic brain injury. One hundred and forty patients with acute traumatic brain injury were enrolled from the neurosurgical departments of three tertiary-level hospitals in China, and the critical illness-related corticosteroid insufficiency incidence, critical-illness-related corticosteroid insufficiency-related risk factors, complications, and 28-day mortality among these patients was recorded. Critical illness-related corticosteroid insufficiency was diagnosed in patients with plasma total cortisol levels less than 10 µg/dL (275.9 nM) on post-injury day 4 or when serum cortisol was insufficiently suppressed (less than 50%) during a dexamethasone suppression test on post-injury day 5. The results demonstrated that critical illness-related corticosteroid insufficiency occurred during the sub-acute phase of traumatic brain injury in 5.6% of patients with mild injury, 22.5% of patients with moderate injury, and 52.2% of patients with severe injury. Traumatic brain injury-induced critical illness-related corticosteroid insufficiency was strongly correlated to injury severity during the sub-acute stage of traumatic brain injury. Traumatic brain injury patients with critical illness-related corticosteroid insufficiency frequently presented with hemorrhagic cerebral contusions, diffuse axonal injury, brain herniation, and hypotension. Differences in the incidence of hospital-acquired pneumonia, gastrointestinal bleeding, and 28-day mortality were observed between patients with and without critical illness-related corticosteroid insufficiency during the sub-acute phase of traumatic brain injury. Hypotension, brain-injury severity, and the types of traumatic brain injury were independent risk factors for traumatic brain injury-induced critical illness-related corticosteroid insufficiency. These findings indicate that critical illness-related corticosteroid insufficiency is common during the sub-acute phase of traumatic brain injury and is strongly associated with poor prognosis. The dexamethasone suppression test is a practical assay for the evaluation of hypothalamic-pituitary-adrenal axis function and for the diagnosis of critical illness-related corticosteroid insufficiency in patients with traumatic brain injury, especially those with hypotension, hemorrhagic cerebral contusions, diffuse axonal injury, and brain herniation. Sub-acute infection of acute traumatic brain injury may be an important factor associated with the occurrence and development of critical illness-related corticosteroid insufficiency. This study protocol was approved by the Ethics Committee of General Hospital of Tianjin Medical University, China in December 2011 (approval No. 201189).

Tauroursodeoxycholic acid prevents ER stress-induced apoptosis and improves cerebral and vascular function in mice subjected to subarachnoid hemorrhage.

Early brain injury (EBI) has been recognized as a major cause of poor clinical outcomes in patients with spontaneous subarachnoid hemorrhage (SAH). Endoplasmic reticulum (ER) stress contributes to EBI, but its impact on cerebrovascular function following SAH remains poorly defined. We tested the hypothesis that blocking ER stress by the inhibitor Tauroursodeoxycholic acid (TUDCA) attenuates EBI, which is associated with the rescue of cerebrovascular function defined by local cerebral blood flow and vascular permeability and ER-stress mediated-apoptosis in mouse models. We first preconditioned mice with TUDCA (500 mg/kg/d × 3 days) before SAH and evaluated them for cerebrovascular function by analyzing cerebral cortical perfusion and blood-brain-barrier (BBB) permeability, unfolded protein response (UPR), ER stress-mediated apoptosis and neurological function after SAH. We found that SAH induced a rapidly reduction in cerebral blood flow and an elevated level of ER stress, which lasted for 24 h. The level of neurological deficits was closely associated with the reduction of cerebral blood flow and excessive ER stress. TUDCA improved cerebral blood flow, reduced BBB permeability, inhibited the ER stress through the PERK/eIF2α/ATF4/CHOP signaling pathway, blocked the Caspase-12-dependent ER-stress mediated apoptosis, resulting in significantly improved neurological function of mice subjected to SAH. These data suggest that blocking ER stress prevents EBI and improves the outcome of mice subjected to experimental SAH. These beneficial effects are associated with the restoration of SAH-associated cerebrovascular dysfunction and reduction of the ER-stress induced apoptosis, but additional signaling pathways of ER stress may also be involved.

Underlying Genes Involved in Atherosclerotic Macrophages: Insights from Microarray Data Mining.

BACKGROUND In an atherosclerotic artery wall, monocyte-derived macrophages are the principal mediators that respond to pathogens and inflammation. The present study aimed to investigate potential genetic changes in gene expression between normal tissue-resident macrophages and atherosclerotic macrophages in the human body. MATERIAL AND METHODS The expression profile data of GSE7074 acquired from the Gene Expression Omnibus (GEO) database, which includes the transcriptome of 4 types of macrophages, was downloaded. Differentially expressed genes (DEGs) were identified using R software, then we performed functional enrichment, protein­protein interaction (PPI) network construction, key node and module analysis, and prediction of microRNAs (miRNAs)/transcription factors (TFs) targeting genes. RESULTS After data processing, 236 DEGs were identified, including 21 upregulated genes and 215 downregulated genes. The DEG set was enriched in 22 significant Gene Ontology (GO) terms and 25 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and the PPI network constructed with these DEGs comprised 6 key nodes with degrees ≥8. Key nodes in the PPI network and simultaneously involved in the prime modules, including rhodopsin (RHO), coagulation factor V (F5), and  bestrophin-1 (BEST1), are promising for the prediction of atherosclerotic plaque formation. Furthermore, in the miRNA/TF-target network, hsa-miR-3177-5p might be involved in the pathogenesis of -atherosclerosis via regulating BEST1, and the transcription factor early growth response-1 (EGR1) was found to be a potential promoter in atherogenesis. CONCLUSIONS The identified key hub genes, predicted miRNAs/TFs, and underlying molecular mechanisms may be involved in atherogenesis, thus potentially contributing to the treatment and diagnosis of patients with atherosclerotic disease.

Estimation and Recanalization of Chronic Occluded Internal Carotid Artery: Hybrid Operation by Carotid Endarterectomy and Endovascular Angioplasty.

OBJECTIVE: Proper treatment for chronic occluded internal carotid artery (ICA) has not been determined. Endovascular recanalization may cause arterial injury and distal embolism. Hybrid recanalization for chronic occluded ICA was performed, and its safety and effectiveness were estimated. METHODS: From March 2011 to March 2017, 21 patients were treated by hybrid recanalization with >1 year of follow-up. The ICA was totally occluded from the cervical segment to the cavernous, ophthalmic, or supraclinoid segment. Clinical characteristics, treatment strategy, recanalization rate, and main adverse events were reviewed retrospectively. RESULTS: Initial recanalization was achieved in 15 patients (71.4%). Successful revascularization was more likely if the ICA was occluded with the plaque at the carotid bifurcation and the thrombus anterograde to the cavernous segment. There was no carotid dissection or intracranial hemorrhage. There were no new postprocedural neurologic deficits. Among 14 patients who underwent successful recanalization with follow-up, 1 patient had a repeat occlusion and another experienced about 50% restenosis. CONCLUSIONS: Hybrid recanalization by carotid endarterectomy and arterial angioplasty is a safe treatment method for chronic totally occluded ICA. Recanalization was more likely to be successful if the ICA was occluded by the plaque at the carotid bifurcation with the thrombus anterograde to the cavernous segment than if the artery was occluded by the plaque at the ophthalmic or supraclinoid segment with the thrombus retrograde to the cervical segment.

Electrical stimulation improved cognitive deficits associated with traumatic brain injury in rats.

Introduction: Cognitive deficits associated with traumatic brain injury (TBI) reduce patient quality of life. However, to date, there have been no effective treatments for TBI-associated cognitive deficits. In this study, we aimed to determine whether electrical stimulation (ES) improves cognitive deficits in TBI rats. Methods: Rats were randomly divided into three groups: the Sham control group, electrical stimulation group (ES group), and No electrical stimulation control group (N-ES group). Following fluid percussion injury, the rats in the ES group received ES treatment for 3 weeks. Potent cognitive function-relevant factors, including the escape latency, time percentage in the goal quadrant, and numbers of CD34+ cells, von Willebrand Factor+ (vWF +) vessels, and circulating endothelial progenitor cells (EPCs), were subsequently assessed using the Morris water maze (MWM) test, immunohistochemical staining, and flow cytometry. Results: Compared with the rats in the N-ES group, the rats in the ES group exhibited a shorter escape latency on day 3 (p = .025), day 4 (p = .011), and day 5 (p = .003), as well as a higher time percentage in the goal quadrant (p = .025) in the MWM test. After 3 weeks of ES, there were increased numbers of CD34+ cells (p = .008) and vWF + vessels (p = .000) in the hippocampus of injured brain tissue in the ES group compared with those in the N-ES group. Moreover, ES also significantly increased the number of EPCs in the peripheral blood from days 3 to 21 after TBI in the ES group (p < .05). Conclusions: Taken together, these findings suggest that ES may improve cognitive deficits induced by TBI, and this protective effect may be a result, in part, of enhanced angiogenesis, which may be attributed to the increased mobilization of EPCs in peripheral blood.

Cold water swimming pretreatment reduces cognitive deficits in a rat model of traumatic brain injury.

A moderate stress such as cold water swimming can raise the tolerance of the body to potentially injurious events. However, little is known about the mechanism of beneficial effects induced by moderate stress. In this study, we used a classic rat model of traumatic brain injury to test the hypothesis that cold water swimming preconditioning improved the recovery of cognitive functions and explored the mechanisms. Results showed that after traumatic brain injury, pre-conditioned rats (cold water swimming for 3 minutes at 4°C) spent a significantly higher percent of times in the goal quadrant of cold water swim, and escape latencies were shorter than for non-pretreated rats. The number of circulating endothelial progenitor cells was significantly higher in pre-conditioned rats than those without pretreatment at 0, 3, 6 and 24 hours after traumatic brain injury. Immunohistochemical staining and Von Willebrand factor staining demonstrated that the number of CD34+ stem cells and new blood vessels in the injured hippocampus tissue increased significantly in pre-conditioned rats. These data suggest that pretreatment with cold water swimming could promote the proliferation of endothelial progenitor cells and angiogenesis in the peripheral blood and hippocampus. It also ameliorated cognitive deficits caused by experimental traumatic brain injury.

The expression of miRNA-221 and miRNA-222 in gliomas patients and their prognosis.

The aim of this study is to explore the expression of microRNA (miRNA)-221 and miRNA-222 in human glioma cells and tissues. The expression of miRNA-221 and miRNA-222 in human glioma cell line U87, U251, A172, LN229 and surgery resected glioma tissues were measured. The survival rate of X-ray (2 Gy) irradiated glioma cells were calculated. 165 cases of glioma patients were recruited successfully; the expression of miRNA-221 and miRNA-222 in their resected tissues were measured. The expression of miRNA-221 and miRNA-222 in cancer tissues were obviously higher than control tissues (normal brain tissue) and control cell (gastric mucosal epithelial cell, GES) (p < 0.05). The highly malignant glioma tissues expressed significantly higher miRNA-221 and miRNA-222 than low malignant glioma tissues. Patients with highly expressed miRNA-221 and miRNA-222 have shorter survival time. Survival rate of glioma cells was significantly higher than GES cell after irradiation (p < 0.05); miRNA-221 in glioma cells. The expressions of miRNA-221 and miRNA-222 in irritated glioma cells were positively correlated with the survival rate of glioma cells (r = 0.629, 0.712, both p < 0.01). For the 165 glioma patients, the expressions of miRNA-221 and miRNA-222 increased with the increasing of pathological grades (χ 2 = 42.85, p < 0.01); and their survival time decreased when miRNA-221 expression elevated (χ 2 = 57.12, p < 0.01). MiRNA-221 and miRNA-222 express highly in human glioma cells and tissues. Expression of miRNA-221 and miRNA-222 are closely related to pathological grading and prognosis of glioma; they could be used as independent prognostic factor for glioma.

Preoperative Visualization of Cranial Nerves in Skull Base Tumor Surgery Using Diffusion Tensor Imaging Technology.

AIM: To visualize cranial nerves (CNs) using diffusion tensor imaging (DTI) with special parameters. This study also involved the evaluation of preoperative estimates and intraoperative confirmation of the relationship between nerves and tumor by verifying the accuracy of visualization. MATERIAL AND METHODS: 3T magnetic resonance imaging scans including 3D-FSPGR, FIESTA, and DTI were used to collect information from 18 patients with skull base tumor. DTI data were integrated into the 3D slicer for fiber tracking and overlapped anatomic images to determine course of nerves. 3D reconstruction of tumors was achieved to perform neighboring, encasing, and invading relationship between lesion and nerves. RESULTS: Optic pathway including the optic chiasm could be traced in cases of tuberculum sellae meningioma and hypophysoma (pituitary tumor). The oculomotor nerve, from the interpeduncular fossa out of the brain stem to supraorbital fissure, was clearly visible in parasellar meningioma cases. Meanwhile, cisternal parts of trigeminal nerve and abducens nerve, facial nerve were also imaged well in vestibular schwannomas and petroclival meningioma cases. The 3D-spatial relationship between CNs and skull base tumor estimated preoperatively by tumor modeling and tractography corresponded to the results determined during surgery. CONCLUSION: Supported by DTI and 3D slicer, preoperative 3D reconstruction of most CNs related to skull base tumor is feasible in pathological circumstances. We consider DTI Technology to be a useful tool for predicting the course and location of most CNs, and syntopy between them and skull base tumor.

miR-21-5p alleviates leakage of injured brain microvascular endothelial barrier in vitro through suppressing inflammation and apoptosis.

Our recent researches have identified increased expression of miR-21-5p in rats brain following traumatic brain injury (TBI), which protected against blood-brain barrier (BBB) damage. To further study the mechanism underlying the role of miR-21-5p on alleviating BBB damage after TBI, we performed the scratch injury model on cultured brain microvascular endothelial cells (BMVECs), which formed the microvascular endothelial barrier - an integral part of the highly specialized BBB. The expression level of miR-21-5p in BMVECs was observed to be increased after scratch injury, and could be further up-regulated by transfecting miR-21-5p mimics. We found that up-regulation of miR-21-5p level in BMVECs can alleviate endothelial barrier damage and loss of tight junction proteins. To further investigate the mechanism of this protective effect, we evaluated the impact of miR-21-5p on inflammation and apoptosis in injured BMVECs. On one hand, miR-21-5p suppressed inflammation by regulating the expression of inflammatory cytokines and NF-kB signaling. On the other hand, miR-21-5p inhibited cellular apoptosis by regulating the expression of apoptosis factors and Akt signaling. In addition, we also detected the activity of Ang-1/Tie-2 axis (associated with BBB stabilization) in BMVECs after scratch injury, and found that miR-21-5p can promote its activation. Taken together, miR-21-5p alleviates leakage of injured brain microvascular endothelial barrier through suppressing inflammation and apoptosis, while impacting the activities of NF-kB, Akt and Ang-1/Tie-2 signaling. Thus, miR-21-5p could be a potential therapeutic target for interventions of BBB damage after TBI.

Retrospective analysis of 620 cases of brain abscess in Chinese patients in a single center over a 62-year period.

BACKGROUND: Despite advances in laboratory diagnostics, antibiotic regimens, and neurosurgical techniques, brain abscess (BA) remains a potentially fatal infectious disease. This study analyzed clinical and epidemiological aspects of BA in Chinese patients treated at a single center during a 62-year period. METHOD: We retrospectively analyzed 620 BA patients treated at Tianjin Medical University General Hospital, Tianjin, PR China from 1952 to 2014. Because of the initiation of imaging technology use in 1992, and other specific changes, we analyzed data over three study periods: 1952-1972, 1980-1991, and 2002-2014. Information including incidence, sex, age, community distribution, BA size and location, therapeutic method, prognosis and outcome of BA patients was collected and evaluated. RESULTS: Our study included 620 BA patients. The percentage mortality significantly decreased from 22.8 % in 1952 to 6.3 % in 2014 (p < 0.001). Although the incidence of BA was higher in males than females, there was no significant change in the male/female incidence ratio over time: 2.5 in 1952-1972, 2.6 in 1980-1991, and 2.2 in 2002-2014. The cryptogenic infection incidence significantly increased over time (p < 0.001). The number of positive bacterial cultures significantly decreased over the three study periods (p < 0.01). CONCLUSIONS: The prognosis of patients with BA has gradually improved over the past 62 years in Tianjin, China. This may be because improvements in neurosurgical techniques, cranial imaging, and antimicrobial regimens have facilitated less invasive and more precise neurosurgical procedures.