Clinical applications of the mastoid emissary vein.

PURPOSE: During retrosigmoid craniotomy, the mastoid emissary vein (MEV) can be a source of considerable bleeding during the operation, especially when the larger diameter MEV or sigmoid sinus is torn. In this study, we evaluated the relevant structure of the MEV for their anatomy and applied the data in surgery to summarize their clinical significance. METHODS: The posterior craniocervical regions of 15 silicon-injected Chinese human cadaver specimens were dissected to expose the MEV and adjacent structures. Fifty-one patients who were scheduled to undergo retrosigmoid craniotomy were selected. All patients underwent preoperative routine CT of the head. The relevant data were collected on cadaveric anatomy and CT. Eventually, all patients underwent retrosigmoid craniotomy and the MEV was observed during the operation. RESULTS: In cadaver specimens, the prevalence of the MEV was 90.0%. It originated from the middle and lower parts of the posterior wall of the sigmoid sinus and extended in the posterior direction in the mastoid process, usually having 1-2 external openings (86.7%) and only 1 internal opening. The intraosseous courses of the MEV were classified as straight and curved. The straight type accounted for 57.9%, and the curved type for 42.1%. The mean diameter of the MEV was 1.84 ± 0.85 mm, and the straight length of the MEV inside the mastoid process was 11.93 ± 3.58 mm. In 16.7% and 6.7% of all cadaver specimens, the MEV diameter was greater than 2.5 and 4 mm, respectively. In 51 patients (bilateral), routine head CT scan showed the MEV in 49.0% of the patients, and the MEV diameter was greater than 2.5 and 4 mm, respectively, in 17.6% (18/102) and 3.9% (4/102) of the cases. During surgery (unilateral) in the 51 patients, 48 had the MEV and 3 had no MEV. None of the patients had sigmoid sinus tears or massive bleeding. CONCLUSION: In the process of retrosigmoid craniotomy, detailed anatomical knowledge of the MEV, well-planned CT scan, and meticulous microsurgical techniques are key for successful operation, which can reduce the occurrence of complications.

Does epilepsy always indicate worse outcomes? A longitudinal follow-up analysis of 485 glioma patients.

BACKGROUND: Epilepsy is one of the most common glioma complications, and the two may be connected in more ways than we understand. We aimed to investigate the clinical features of glioma-associated epilepsy and explore the risk factors associated with it. METHODS: We collected clinical information from 485 glioma patients in the Nanjing Brain Hospital and conducted 4 periodic follow-up visits. Based on the collected data, we analyzed the clinical characteristics of glioma patients with or without epilepsy and their relationship with survival. RESULTS: Among glioma patients, younger people were more likely to have epilepsy. However, epilepsy incidence was independent of gender. Patients with grade II gliomas were most likely to develop epilepsy, while those with grade IV gliomas were least likely. There was no difference in Karnofsky Performance Status scores between patients with glioma-associated epilepsy and those without epilepsy. Additionally, epilepsy was independently associated with longer survival in the World Health Organization grade IV glioma patients. For grades II, III, and IV tumors, the 1-year survival rate of the epilepsy group was higher than that of the non-epilepsy group. CONCLUSIONS: Epilepsy did not lead to worse admission performance and correlated with a better prognosis for patients with grade IV glioma.

A clinical report of intracranial granulocytic sarcoma and a literature review.

BACKGROUND: Granulocytic sarcoma (GS), is also referred to as myeloid sarcoma. It is a solid mass formed by the primitive or immature myeloid cells extramedullary infiltration, which is commonly caused by acute myelogenous leukemia (AML) or chronic myelogenous leukemia (CML). It mainly involves bones, lymph nodes, skin and soft tissues of the head and neck. In general, the incidence is low and central nervous system (CNS) involvement is relatively rare. The clinical manifestations of the disease are varied and the treatment is intractable. CASE DESCRIPTION: A 53-year-old male with intracranial granulocytic sarcoma who suffered a pressing pain on the left cheek. The patient had a hypophasis with left corneal reflex diminished. He had bilateral anisocoria, lower jaw and tongue tilted to the left upon opening the mouth and the left pharyngeal reflex was declined. The whole blood routine was normal except for eosinophils, head magnetic resonance imaging plain scan revealed a space-occupying lesion. Postoperative pathology suggested GS. Unfortunately, the disease progressed quickly and the patient died. CONCLUSION: Isolated GS is often difficult to diagnose accurately. The patient's medical history should be carefully reviewed, all relevant tests should be performed, and various differential diagnoses should be familiarized with to improve the accuracy of diagnosis. And on this basis, to develop a personalized treatment plan for different patients.

De-differentiation associated with drop metastasis of a recurrent intracranial solitary fibrous tumor: a case report and literature review.

BACKGROUND: Central nervous system is a rare occurring location of solitary fibrous tumors (SFTs). SFTs have a potential for recurrence, which is the leading cause of death in patients with these disease entities. De-differentiation phenomenon combined with cerebrospinal fluid (CSF) dissemination through drop metastasis of STFs from intracranial to intraspinal has only been reported in extremely limited cases. CASE DESCRIPTION: Herein, we present a case of SFT in a 54-year old male. MRI showed characteristic of mixed high and low signal with 6.3 cm × 6.5 cm × 5.9 cm. After radical surgical resection, the pathology indicated benign SFT. However, MRI re-examination of 22 months later detected local recurrence, concomitant with spreading of intracranial and intraspinal through CSF dissemination. And interestingly, the second pathology found de-differentiation phenomenon and malignance of SFT, in which some areas transformed to rhabdomyosarcoma. CONCLUSION: This is the first case report of recurrent intracranial SFT de-differentiating to rhabdomyosarcoma concurrent with CSF pathway drop metastasis. Benign intracranial SFTs have the potential of de-differentiation, which may play an important role in its distant metastasis. The underlying molecular biological and pathological mechanisms of benign SFT malignance transformation still warrant further exploration.

FTY720 Reduces Endothelial Cell Apoptosis and Remodels Neurovascular Unit after Experimental Traumatic Brain Injury.

Traumatic brain injury (TBI) is a major cause of death and disability worldwide. A sequence of pathological processes occurred when there is TBI. Previous studies showed that sphingosine-1-phosphate receptor 1 (S1PR1) played a critical role in inflammatory response in the brain after TBI. Thus, the present study was designed to evaluate the effects of the S1PR1 modulator FTY720 on neurovascular unit (NVU) after experimental TBI in mice. The weight-drop TBI method was used to induce TBI. Western blot (WB) was performed to determine the levels of SIPR1, claudin-5 and occludin at different time points. FTY720 was intraperitoneally administered to mice after TBI was induced. The terminal deoxynucleotidyl transferase-dUTP nick end labeling (TUNEL) assay was used to assess endothelial cell apoptosis. Immunofluorescence and WB were performed to measure the expression of tight junction proteins: claudin-5 and occludin. Evans blue (EB) permeability assay and brain water content were applied to evaluate the blood-brain barrier (BBB) permeability and brain edema. Immunohistochemistry was performed to assess the activation of astrocytes and microglia. The results showed that FTY720 administration reduced endothelial cell apoptosis and improved BBB permeability. FTY720 also attenuated astrocytes and microglia activation. Furthermore, treatment with FTY720 not only improved neurological function, but also increased the survival rate of mice significantly. These findings suggest that FTY720 administration restored the structure of the NVU after experimental TBI by decreasing endothelial cell apoptosis and attenuating the activation of astrocytes. Moreover, FTY720 might reduce inflammation in the brain by reducing the activation of microglia in TBI mice.

Spontaneous acute epidural hematoma associated with chronic subdural hematoma due to dural metastasis of gastric carcinoma: a case report and literature review.

Background: Non-traumatic spontaneous acute epidural hematoma (EDH) happening to chronic subdural hematoma (SDH) caused by dural metastases is a rare entity. Pathogenesis can be derived from infection, coagulopathy, and inflammation. Malignant tumors metastasize to dura mater is one of the most infrequent causes. The exact mechanism remains elusive in spite of several possible speculations. The clinical manifestations, management and outcomes vary among reported cases.Case Description: A 45-year-old woman without history of trauma presented with headache, vomiting and disturbance of consciousness and developed brain hernia rapidly. On arival, she has lost into coma with Glasgow coma scale (GCS) score 5, bilateral pupils were not equal, with disappeared reflectance. Emergency imaging prompted large acute EDH, combined with SDH, arising from dural granular neoplasm confirmed intraoperatively. Four days after surgery, the bilateral pupils were equal in size and sensitive to light reflection.Conclusion: Dural metastases can cause EDH, chronic SDH can also be resulted from metastatic tumors of dura mater. When dealing with spontaneous non-traumatic hematoma around the dura mater, to make the precise diagnosis is sometimes doubtful and confusing. The stream of diagnostic thinking should be opened, including medical diseases such as liver and kidney disease, drug history, history of cancer and other possible clues. Thus, a detailed and purposeful systematic medical history review and physical examination is important in order to make more appropriate strategies for the clinic.

Intracranial solitary fibrous tumor/hemangiopericytomas: a clinical analysis of a series of 17 patients.

OBJECTIVE: Solitary fibrous tumors (SFTs) and haemangiopericytomas (HPCs) are rare mesenchymal tumors in central nervous system (CNS). Although progressed recognition to the diagnosis and treatment of SFT/HPCs, it still remains many confusions regarding on its occurrence, aggressive evolution, malignant transformation, dedifferentiation phenomenon, distant metastasis and unpredictable propensity. PATIENTS AND METHODS: Seventeen cases of CNS SFT/HPCs who underwent surgical treatment from January 2010 to December 2020 were collected in the authors' institute. Clinical, radiological, pathological data and followup details were reviewed in all cases. RESULTS: The age of this series was 41-73 years old. Seven cases located subtentorially, five cases originated from middle skull base and four in supratentorial. MRI shows iso-signal intensity on T1WI, and heterogeneous slightly long/short signal on T2WI. There is significant contrast after gadolinium-enhancement. It is easy to be misdiagnosed before surgery. The positive rate of nuclear STAT6 is 94.12%, higher than CD34 (87.5%). Eight patients were grade I, eight grade II and one in grade III. Five cases developed tumor relapse, in which two cases had local intracranial recurrence combined with dissemination and metastasis of cerebrospinal fluid in the spinal canal, accompanied by pathological malignant transformation, and another one occurred blood metastasis. CONCLUSIONS: CNS SFT/HPCs are rare intracranial tumors with unpredictable propensity. Gross total resection is critical to its overall clinical prognosis. Given its potential recurrence and malignant transition, adjuvant radiotherapies are recommended when necessary, and long-term follow-up is indispensable. The underlying molecular biological mechanisms are still needed to be further exploration.

The anatomy of the parapharyngeal segment of the internal carotid artery for endoscopic endonasal approach.

Injury to the internal carotid artery (ICA) is a life-threatening complication of endoscopic endonasal approaches. The objective of this study is to illustrate the detail anatomy of the parapharyngeal segment of the ICA (PPICA) to safe endoscopic endonasal surgery. The anatomical dissection was performed in 10 cadaveric specimens and several crucial anatomical landmarks were identified and measured. In addition, 50 dry skulls were studied to further assess the relationship between the pharyngeal tubercle and carotid foramen. From the endoscopic endonasal perspective, in the median plane, the pharyngeal tubercle and the carotid foramen on both sides were located on a line. The average distance between the pharyngeal tubercle and anterior border of the external orifice of the carotid canal was measured as 25.2 ± 3.2 mm. In the paramedian plane, the PPICA was located between the levator veli palatini muscle (LVPM) and the stylopharyngeal muscle (SPM) in upper parapharyngeal space in all specimens, and the distance from the posterior border of the LVPM to the anterior border of the SPM was recorded as 15.1 ± 2.8 mm at the level of the carotid foramen. The distance from the attachment of the LVPM to the anterior border of the external orifice of the carotid canal was about 5.1 ± 0.2 mm. The fully developed stylopharyngeal fascia (SPhF) was observed in 10 cases, and the PPICA was always anteriorly enclosed by and adhered to the SPhF.

Lentivirus mediated γ-interferon-inducible lysosomal thiol reductase (GILT) knockdown suppresses human glioma U373MG cell proliferation.

BACKGROUND: Glioma is the most common malignancy in brain carcinoma with poor prognosis due to the lack of understanding of the mechanism underlying the disease. γ-interferon-inducible lysosomal thiol reductase (GILT) plays a critical role in the process of antigen processing. However, the role of GILT in the tumorigenesis of glioma remains unknown. MATERIALS AND METHODS: The expression of GILT was analyzed by bioinformatics using the public database and by qPCR in three human glioma cell lines. Cell growth and viability were determined by Celigo and MTT assays, while cell cycle arrest and apoptosis were determined using flow cytometry. Giemsa staining was used to analyze the colony formation, while cell motility was assessed using transwell migration and invasion assays, as well as, using tumor growth in nude mice. RESULTS: GILT was highly expressed as observed in the public database on human gliomas and two human glioma cell lines, U373MG and U87MG cells. The downregulation of GILT by lentiviral-mediated silencing inhibits the cell growth, colony formation, and migration but promotes apoptosis and results in cell cycle arrest at the G0/G1 phase in the U373MG cells. Also, the knockdown of GILT inhibits tumor growth in vivo. CONCLUSION: Elevated GILT is positively associated with glioma progression. GILT silencing suppresses cell proliferation, colony formation, migration, and tumor growth, and induces apoptosis and cell cycle arrest. GILT may serve as a potential target for the treatment of glioma.

K6PC-5 Activates SphK1-Nrf2 Signaling to Protect Neuronal Cells from Oxygen Glucose Deprivation/Re-Oxygenation.

BACKGROUND/AIMS: New strategies are required to combat neuronal ischemia-reperfusion injuries. K6PC-5 is a novel sphingosine kinase 1 (SphK1) activator whose potential activity in neuronal cells has not yet been tested. METHODS: Cell survival and necrosis were assessed with a Cell Counting Kit-8 assay and lactate dehydrogenase release assay, respectively. Mitochondrial depolarization was tested by a JC-1 dye assay. Expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling components were examined by quantitative real-timePCR and western blotting. RESULTS: K6PC-5 protected SH-SY5Y neuronal cells and primary murine hippocampal neurons from oxygen glucose deprivation/re-oxygenation (OGDR). K6PC-5 activated SphK1, and SphK1 knockdown by targeted short hairpin RNA (shRNA) almost completely abolished K6PC-5-induced neuronal cell protection. Further work showed that K6PC-5 inhibited OGDR-induced programmed necrosis in neuronal cells. Importantly, K6PC-5 activated Nrf2 signaling, which is downstream of SphK1. Silencing of Nrf2 by targeted shRNA almost completely nullified K6PC-5-mediated neuronal cell protection against OGDR. CONCLUSION: K6PC-5 activates SphK1-Nrf2 signaling to protect neuronal cells from OGDR. K6PC-5 might be a promising neuroprotective strategy for ischemia-reperfusion injuries.

Four-octyl itaconate activates Keap1-Nrf2 signaling to protect neuronal cells from hydrogen peroxide.

BACKGROUND: Four-octyl itaconate (OI), the itaconate's cell-permeable derivative, can activate Nrf2 signaling via alkylation of Keap1 at its cysteine residues. The current study tested the potential neuroprotective function of OI in hydrogen peroxide (H2O2)-treated neuronal cells. METHODS: SH-SY5Y neuronal cells and epigenetically de-repressed (by TSA treatment) primary murine neurons were treated with OI and/or H2O2. Nrf2 pathway genes were examined by Western blotting assay and real-time quantitative PCR analysis. Neuronal cell death was tested by the LDH and trypan blue staining assays. Apoptosis was tested by TUNEL and Annexin V assays. RESULTS: In SH-SY5Y neuronal cells and primary murine neurons, OI activated Nrf2 signaling, causing Keap1-Nrf2 disassociation, Nrf2 protein stabilization and nuclear translocation, as well as expression of Nrf2-regulated genes (HO1, NQO1 and GCLC) and ninjurin2 (Ninj2). Functional studies showed that OI attenuated H2O2-induced reactive oxygen species (ROS) production, lipid peroxidation and DNA damage as well as neuronal cell death and apoptosis. shRNA-mediated knockdown, or CRISPR/Cas9-induced knockout of Nrf2 almost abolished OI-induced neuroprotection against H2O2. Keap1 is the primary target of OI. Keap1 knockout by CRISPR/Cas9 method mimicked and abolished OI-induced actions in SH-SY5Y cells. Introduction of a Cys151S mutant Keap1 in SH-SY5Y cells reversed OI-induced Nrf2 activation and anti-H2O2 neuroprotection. CONCLUSIONS: OI activates Keap1-Nrf2 signaling to protect SH-SY5Y cells and epigenetically de-repressed primary neurons from H2O2 in vitro.

AntagomiR-613 protects neuronal cells from oxygen glucose deprivation/re-oxygenation via increasing SphK2 expression.

Oxygen glucose deprivation (OGD)/re-oxygenation (OGDR) causes damages to neuronal cells. Sphingosine kinase 2 (SphK2) expression could exert neuroprotective functions. Here, we aim to induce SphK2 expression via inhibiting the anti-SphK2 microRNA: microRNA-613 ("miR-613"). In both SH-SY5Y neuronal cells and primary murine hippocampal neurons, transfection of the miR-613's specific inhibitor, antagomiR-613 ("antamiR-613"), induced miR-613 depletion and SphK2 expression. Reversely, forced over-expression of miR-613 caused SphK2 downregulation in SH-SY5Y cells. OGDR-induced cytotoxicity in neuronal cells was largely attenuated by antamiR-613. SphK2 is required for antamiR-613-induced actions in neuronal cells. SphK2 knockdown (by targeted-shRNAs) or inhibition (by its inhibitor ABC294640) almost completely abolished antamiR-613-mediated neuroprotection against OGDR. Further studies showed that OGDR-induced reactive oxygen species (ROS) production, lipid peroxidation, and DNA damages in SH-SY5Y cells were largely attenuated by antamiR-613, but were intensified by miR-613 expression. Taken together, we conclude that antamiR-613 protects neuronal cells from OGDR probably via inducing SphK2 expression.

An in vitro-transcribed circular RNA targets the mitochondrial inner membrane cardiolipin to ablate EIF4G2+/PTBP1+ pan-adenocarcinoma.

In vitro-transcribed (IVT) mRNA has arisen as a rapid method for the production of nucleic acid drugs. Here, we have constructed an oncolytic IVT mRNA that utilizes human rhinovirus type 2 (HRV2) internal ribosomal entry sites (IRESs) to selectively trigger translation in cancer cells with high expression of EIF4G2 and PTBP1. The oncolytic effect was provided by a long hGSDMDc .825 T>A/c.884 A>G-F1LCT mutant mRNA sequence with mitochondrial inner membrane cardiolipin targeting toxicity that triggers mitophagy. Utilizing the permuted intron-exon (PIE) splicing circularization strategy and lipid nanoparticle (LNP) encapsulation reduced immunogenicity of the mRNA and enabled delivery to eukaryotic cells in vivo. Engineered HRV2 IRESs-GSDMDp.D275E/E295G-F1LCT circRNA-LNPs (GSDMDENG circRNA) successfully inhibited EIF4G2+/PTBP1+ pan-adenocarcinoma xenografts growth. Importantly, in a spontaneous tumor model with abnormal EIF4G2 and PTBP1 caused by KRAS G12D mutation, GSDMDENG circRNA significantly prevented the occurrence of pancreatic, lung and colon adenocarcinoma, improved the survival rate and induced persistent KRAS G12D tumor antigen-specific cytotoxic T lymphocyte responses.

Case report: a case of primary intracranial parasagittal meningeal angiosarcoma.

BACKGROUND: Angiosarcoma, also known as malignant hemangioendothelioma, is a rare vasogenic malignant tumor, commonly found on the skin of the head and neck, rarely occurring in the intracranial region. As for intracranial meningeal angiosarcoma, only 8 cases have been reported before and there is no clinical study with large sample size. We report here a case of parasagittal meningeal angiosarcoma. CASE DESCRIPTION: A 48-year-old Chinese male patient was admitted to our hospital due to headache accompanied by bilateral lower limb weakness. On admission, CT showed a high-density mass on both sides of the sagittal sinus at the top of the frontal lobe. We performed exploratory surgical resection of the tumor. During the operation, it was found that the tumor originated from the dura mater and extensively invaded the surrounding brain tissue and skull, and the surrounding hemosiderin deposition was observed. Postoperative pathology suggested angiosarcoma. CONCLUSIONS: Intracranial meningeal angiosarcoma is difficult to accurately diagnose before surgery, so radiologists and neurosurgeons need to strengthen their understanding of this disease. The presence of extensive superficial hemosiderin deposition during operation may contribute to the diagnosis, and immunohistochemistry is very important for the diagnosis of intracranial angiosarcoma.

Modified Skin Incision and Location of Burr-Hole Surgery via a Retrosigmoid Approach: An Anatomical Study.

Objective This study aims to reduce the tissue damage during craniotomy with retrosigmoid approach. A modified sickle-shaped skin incision was developed, and a new burr-hole positioning method was proposed. Methods Five adult cadaveric heads (10 sides) were used in this study. The sickle-shaped skin incision was performed during craniotomy. The nerves, blood vessels, and muscles were observed and measured under a microscope. Additionally, 62 dry adult skull specimens (left sided, n = 35; right sided, n = 27) were used to measure the distance between the most commonly used locating point (asterion [Ast] point) and the posteroinferior point of the transverse sigmoid sinus junction (PSTS) (Ast-PSTS), as well as the distance between the new locating O point and the PSTS (O-PSTS). Then, the reliability of the new locating O point was validated on the same five adult cadaveric heads (10 sides) used for the sickle-shaped skin incision. Results The sickle-shaped skin incision reduced the damage to the occipital nerves, blood vessels, and muscles during the surgery via a retrosigmoid approach. The dispersion and variability of O-PSTS were smaller than those of Ast-PSTS. Conclusion The sickle-shaped skin incision of the retrosigmoid approach can reduce the tissue damage and can completely expose the structures in the cerebellopontine angle. The modified O point is a more reliable locating point for a burr-hole surgery than the Ast point.

Primary salivary acinar cell carcinoma of the parotid gland with parietal skull metastasis: A case report.

Acinar cell carcinoma of the salivary gland (AciCC) is a rare low-grade epithelial malignant tumor of the salivary gland. The primary site of the disease is often in the parotid gland, followed by the submandibular gland and small salivary gland. In the early stage of the disease, there are no obvious symptoms, most of which are slow enlargement of the mass, accompanied by local pain or discomfort, or facial paralysis involving the facial nerve. Although the disease is a low-grade malignant tumor, it is invasive to a certain extent and prone to recurrence and metastasis. The metastasis sites are usually liver, lung, stomach and other visceral organs, while the metastasis of brain and skull is rarely reported by other authors. This paper reports a case of skull tumors, unlike other skull tumors, the patients had typical clinical manifestations and imaging findings are not ideal at the same time, considering the history of patients with parotid gland tumor, in the process of diagnosis for us to produce a large disturbance, single-shot, due to the lesions in the exclusion of the patients with other diseases, we decided to surgery was performed in patients with the treatment, The patient's condition improved after surgical treatment and was diagnosed as salivary adenocarcinoma with skull metastasis by pathology. This article summarizes the diagnosis and treatment of the patient, and summarizes some of the author's treatment experience, in order to increase the understanding of the disease, improve the accuracy of diagnosis, and accumulate relevant clinical experience.

Altered Structural and Functional Patterns Within Executive Control Network Distinguish Frontal Glioma-Related Epilepsy.

Background: The tumor invasion of the frontal lobe induces changes in the executive control network (ECN). It remains unclear whether epileptic seizures in frontal glioma patients exacerbate the structural and functional alterations within the ECN, and whether these changes can be used to identify glioma-related seizures at an early stage. This study aimed to investigate the altered structural and functional patterns of ECN in frontal gliomas without epilepsy (non-FGep) and frontal gliomas with epilepsy (FGep) and to evaluate whether the patterns can accurately distinguish glioma-related epilepsy. Methods: We measured gray matter (GM) volume, regional homogeneity (ReHo), and functional connectivity (FC) within the ECN to identify the structural and functional changes in 50 patients with frontal gliomas (29 non-FGep and 21 FGep) and 39 healthy controls (CN). We assessed the relationships between the structural and functional changes and cognitive function using partial correlation analysis. Finally, we applied a pattern classification approach to test whether structural and functional abnormalities within the ECN can distinguish non-FGep and FGep from CN subjects. Results: Within the ECN, non-FGep and FGep showed increased local structure (GM) and function (ReHo), and decreased FC between brain regions compared to CN. Also, non-FGep and FGep showed differential patterns of structural and functional abnormalities within the ECN, and these abnormalities are more severe in FGep than in non-FGep. Lastly, FC between the right superior frontal gyrus and right dorsolateral prefrontal cortex was positively correlated with episodic memory scores in non-FGep and FGep. In particular, the support vector machine (SVM) classifier based on structural and functional abnormalities within ECN could accurately distinguish non-FGep and FGep from CN, and FGep from non-FGep on an individual basis with very high accuracy, area under the curve (AUC), sensitivity, and specificity. Conclusion: Tumor invasion of the frontal lobe induces local structural and functional reorganization within the ECN, exacerbated by the accompanying epileptic seizures. The ECN abnormalities can accurately distinguish the presence or absence of epileptic seizures in frontal glioma patients. These findings suggest that differential ECN patterns can assist in the early identification and intervention of epileptic seizures in frontal glioma patients.

RhoJ facilitates angiogenesis in glioblastoma via JNK/VEGFR2 mediated activation of PAK and ERK signaling pathways.

Glioblastoma (GBM) is a highly vascularized malignant tumor that depends on new blood vessel formation. Small molecules targeting the angiogenic process may be an effective anti-GBM therapeutic strategy. We previously demonstrated that RhoJ promoted the progression and invasion of GBM. RhoJ has also been shown to be expressed in endothelial cells and plays an important role in regulating endothelial cell migration and tumor angiogenesis. Therefore, we aimed to evaluate the role and mechanism of actions of RhoJ in GBM angiogenesis. We analyzed the expression of RhoJ in different grade gliomas and investigated its role in GBM angiogenesis in vivo and in vitro. Furtherly, RNA sequencing (RNA-seq), Western blotting and immunofluorescence were performed to identify the molecular mechanism of RhoJ in regulating endothelial cell behavior and GBM angiogenesis. Here, we found that silencing RhoJ resulted in inhibition of HUVEC cell migration and blood vessel formation. Overexpression of RhoJ promoted the expression of CD31, EpCAM and moesin, suggesting RhoJ facilitated angiogenesis and the malignant progression of GBM. RNA-seq data showed that VEGF/TNF signaling pathway positively regulated RhoJ. The expression levels of RhoJ was upregulated with the stimulation of VEGF, and reduced by the treatment of JNK inhibitor SP600125. It was also found that the activity of PAK-BRAF-ERK was down-regulated upon RhoJ and JNK knockdown. In conclusion, these results suggested that RhoJ plays an essential role in regulating GBM angiogenesis through the JNK/VEGFR2-PAK-ERK signaling pathway and there might exist a VEGF-JNK/ERK-VEGF circuitry. Thus, RhoJ may be a candidate therapeutic target for anti-angiogenesis treatment in GBM.

Inhibition of TRPA1 Attenuates Oxidative Stress-induced Damage After Traumatic Brain Injury via the ERK/AKT Signaling Pathway.

Neuron apoptosis is a feature of secondary injury after traumatic brain injury (TBI). Evidence implies that excess calcium (Ca2+) ions and reactive oxidative species (ROS) play critical roles in apoptosis. In reaction to increased ROS, the anti-oxidative master transcription factor, Transient receptor potential Ankyrin 1 (TRPA1) allows Ca2+ ions to enter cells. However, the effect of TBI on the expression of TRPA1 and the role of TRPA1 in TBI are unclear. In the present study, TBI in the mouse brain was simulated using the weight-drop model. The process of neuronal oxidative stress was simulated in HT22 neuronal cells by treatment with hydrogen peroxide. We found that TRPA1 was significantly upregulated in neurons at 24 h after TBI. Neuronal apoptosis was increased in the in vivo and in vitro models; however, this increase was reduced by the functional inhibition of TRPA1 in both models. After TBI, TRPA1 was upregulated via nuclear factor, erythroid 2 like 2 (Nrf2) in neurons. TRPA1-mediated neuronal apoptosis after TBI might be achieved in part through the CaMKII/AKT/ERK signaling pathway. To sum up, TBI-triggered TRPA1 upregulation in neurons is mediated by Nrf2 and the functional blockade of TRPA1 attenuates neuronal apoptosis and improves neuronal dysfunction, partially mediated through the activation of the calcium/calmodulin dependent protein kinase II (CaMKII) extracellular regulated kinase (ERK)/protein kinase B (AKT) signaling pathway. Our results suggest that functional blockade of TRPA1 might be a promising therapeutic intervention related to ROS and Nrf2 in TBI.

Risk Factors for Postoperative Rebleeding and Short-Term Prognosis of Spontaneous Cerebellar Hemorrhage.

PURPOSE: Postoperative rebleeding (PRB) is one of the most severe complications after hematoma evacuation of spontaneous intracerebral hemorrhage (ICH). PRB has been proven to be an independent risk factor for poor prognosis. Previous studies have shown that spot sign and blend sign are independent risk factors for PRB of spontaneous ICH. However, the risk factors for PRB of spontaneous cerebellar hemorrhage (SCH) have not been elucidated. The aim of the present study was to investigate the possible risk factors for PRB and short-term prognosis of patients with SCH. PATIENTS AND METHODS: This study identified 62 patients with SCH who underwent hematoma evacuation in our department. Risk factors for PRB and short-term prognosis were identified by a univariable logistic regression model, and predictors with a P value of less than 0.05 were included in the multivariable logistic regression model to identify independent predictors. A receiver operating characteristic (ROC) curve was created to test the sensitivity and specificity of independent risk factors. RESULTS: Hematoma volume was the only independent predictor of PRB (OR=15.14, 95% CI=1.08-213.1, P=0.044). The sensitivity and specificity of hematoma volume to PRB were 63.6% and 89.7%, respectively, and the cutoff value of hematoma volume was >29.3 mL. GCS score ≤8 (OR=5.131, 95% CI=1.030-25.554, P=0.046) and PRB (OR=13.17, 95% CI=1.316-131.798, P=0.028) were independent risk factors for poor prognosis of patients with SCH. The sensitivity and specificity of the GCS score to poor prognosis were 66.7% and 86.2%, respectively. The sensitivity and specificity of the PRB to poor prognosis were 36.4% and 96.6%, respectively. CONCLUSION: Hematoma volume is likely to be a strong predictor of PRB among patients with SCH. GCS scores ≤8 on arrival and PRB were significant predictors of short-term poor outcome.