Long-term Efficacy of Bilateral Globus Pallidus Stimulation in the Treatment of Meige Syndrome.

OBJECTIVE: This study aimed to investigate the long-term efficacy and prognosis of bilateral globus pallidus internus (GPi) deep brain stimulation (DBS) in patients with benign essential blepharospasm (BEB) and complete Meige syndrome, and to search for the best therapeutic subregion within the GPi. MATERIALS AND METHODS: Data were collected for 36 patients with Meige syndrome who underwent bilateral GPi-DBS surgery at our hospital between March 2014 and February 2022. Using the Burk-Fahn-Marsden Dystonia Rating Scale (BFMDRS)-Movement (BFMDRS-M) and BFMDRS-Disability (BFMDRS-D), the severity of the symptoms of patients with complete Meige syndrome was evaluated before surgery and at specific time points after surgery. Patients with BEB were clinically evaluated for the severity of blepharospasm using BFMDRS-M, the Blepharospasm Disability Index (BDI), and Jankovic Rating Scale (JRS). Three-dimensional reconstruction of the GPi-electrode was performed in some patients using the lead-DBS software, and the correlation between GPi subregion volume of tissue activated (VTA) and symptom improvement was analyzed in patients six months after surgery. The follow-up duration ranged from six to 99 months. RESULTS: Compared with preoperative scores, the results of all patients at six months after surgery and final follow-up showed a significant decrease (p < 0.05) in the mean BFMDRS-M score. Among them, the average BFMDRS-M improvement rates in patients with BEB at six months after surgery and final follow-up were 60.3% and 69.7%, respectively, whereas those in patients with complete Meige syndrome were 54.5% and 58.3%, respectively. The average JRS and BDI scores of patients with BEB also decreased significantly (p < 0.05) at six months after surgery and at the final follow-up (JRS improvement: 38.6% and 49.1%, respectively; BDI improvement: 42.6% and 57.4%, respectively). We were unable to identify significantly correlated prognostic factors. There was a significant correlation between GPi occipital VTA and symptom improvement in patients at six months after surgery (r = 0.34, p = 0.025). CONCLUSIONS: Our study suggests that bilateral GPi-DBS is an effective treatment for Meige syndrome, with no serious postoperative complications. The VTA in the GPi subregion may be related to the movement score improvement. In addition, further research is needed to predict patients with poor surgical outcomes.

HCN1 pathogenic variants associated with childhood epilepsy in a cohort of Chinese patients.

OBJECTIVE: HCN ion channel family has a widespread expression in neurons, and recently, increasing studies have demonstrated their roles in epilepsies. METHODS: Clinical data of the patients were gathered in a retrospective study. Exon sequencing was used for the patients with unexplained recurrent seizures and varying levels of developmental delay. RESULTS: In this study, eight de novo variants of HCN1 genes were uncovered in eight patients, including six missense variants, one nonsense variant and one frameshift insertion variant; five of them were reported for the first time. The onset age for eight patients ranges from one month to one year. Their main clinical manifestations are epilepsy and varying degrees of developmental delay, and the main type of seizure is focal secondary generalized tonic-clonic seizure. Importantly, in our study, one case presented with a form of migrating focal seizure that has not been reported in the literature. Seizures from five of the eight children were effectively controlled with antiepileptic drugs including valproic acid, levetiracetam and oxcarbazepine. One child developed normally and four children developed mild delay. One child was treated with topiramate, and the convulsion was partially controlled and showed moderate to severe developmental delay. The antiepileptic treatment failed for the other two children, and the two children were treated with sodium valproate, oxcarbazepine, lamotrigine, chlorbazan, levetiracetam and nitrodiazepam successively, but their convulsions were not controlled and showed moderate to severe developmental delay. SIGNIFICANCE: Our research reported eight variants in HCN1 gene causing epilepsy; among these variants, five variants were never reported before. HCN1-related epilepsy usually starts infantile period, and focal secondary generalized tonic-clonic seizure is the most common seizure type. Importantly, we reported the case with migrating focal seizure was rarely reported. Our study expanded both genotype and phenotype for HCN1-related epilepsy.

Predictors of seizure outcomes in patients with diffuse low-grade glioma-related epilepsy after complete glioma removal.

AIMS: We aimed to identify predictors of postoperative seizures in patients with diffuse low-grade glioma (DLGG)-related epilepsy after complete tumor resection in this study. METHODS: We retrospectively collected data from individuals with DLGG-related epilepsy whose tumors were completely resected at Xiangya Hospital, Central South University between January 2014 and January 2020. The predictors of seizure outcomes were assessed by employing univariate analysis and a multivariate logistic regression model in a backward binary logistic regression model. RESULTS: Among the 118 cases that met the inclusion criteria, 83.05% were seizure-free following an average follow-up of 4.27 ± 1.65 years, all of whom were classified as International League Against Epilepsy class I outcome. Univariate and multivariate analyses indicated that seizure duration of >6 years (odds ratio [OR], 6.62; 95% confidence interval [CI], 1.76-24.98; p = 0.005) and first clinical symptoms other than seizures (OR, 4.51; 95% CI, 1.43-14.23; p = 1.010) were both independent predictors of unfavorable seizure outcomes. CONCLUSION: Our results imply that satisfactory seizure outcomes can be achieved in most patients with DLGG-related epilepsy after complete tumor resection. Patients with seizure duration of >6 years or first clinical symptoms other than seizures were more likely to experience postoperative seizure recurrence.

Resective surgery for patients with frontal lobe diffuse low-grade glioma-related epilepsy: predictors of seizure outcomes.

Background: Diffuse low-grade gliomas (DLGGs) are prone to invade the frontal lobes, with seizures being the most common symptom. However, limited attention has been paid to surgical outcomes and their predictors in patients with frontal DLGG-related epilepsy. Objective: This study aimed to analyze predictors of postoperative seizure outcomes in patients with frontal DLGG-related epilepsy. Design: This is a single-center retrospective study. Methods: This study retrospectively collected data of 115 patients with frontal DLGG-related epilepsy who underwent resective surgery between January 2014 and January 2021. Patients were categorized into favorable and unfavorable seizure outcome groups based on the International League Against Epilepsy (ILAE) classification. Univariate and multivariate analyses were used to identify potential predictors of seizure outcomes. Results: The mean follow-up was 4.11 ± 2.06 years, and 77.4% (89 of 115) of patients were seizure-free. Permanent neurological deficits were observed in 7.0% (8 of 115) of patients. Univariate and multivariate analyses revealed that total tumor removal [odds ratio (OR), 0.31; 95% confidence interval (CI), 0.12-0.82; p = 0.018] and older age at seizure onset (OR, 0.96; 95% CI, 0.93-0.99; p = 0.042) were independent predictors of favorable seizure outcomes. Conclusion: Surgical resection is an effective treatment for frontal DLGG-related epilepsy. Favorable seizure outcomes are more likely to be achieved in patients with complete tumor removal and those with older age at seizure onset.

Genetically proxied gut microbiota, gut metabolites with risk of epilepsy and the subtypes: A bi-directional Mendelian randomization study.

Background: An increasing number of observational studies have revealed an association among the gut microbiota, gut metabolites, and epilepsy. However, this association is easily influenced by confounders such as diet, and the causality of this association remains obscure. Methods: Aiming to explore the causal relationship and ascertain specific gut microbe taxa for epilepsy, we conducted a bi-directional Mendelian randomization (MR) study based on the genome-wide association study (GWAS) data of epilepsy from the International League Against Epilepsy, with the gut microbiota GWAS results from MiBioGen, and summary-level GWAS data of gut microbiota-dependent metabolites trimethylamine N-oxide and its predecessors. Results: Nine phyla, 15 classes, 19 orders, 30 families, and 96 genera were analyzed. A suggestive association of host-genetic-driven increase in family Veillonellaceae with a higher risk of childhood absence epilepsy (odds ratio [OR]: 1.033, confidential interval [CI]: 1.015-1.051, P IVW = 0.0003), class Melainabacteria with a lower risk of generalized epilepsy with tonic-clonic seizures (OR = 0.986, CI = 0.979-0.994, P IVW = 0.0002), class Betaproteobacteria (OR = 0.958, CI = 0.937-0.979, P IVW = 0.0001), and order Burkholderiales (OR = 0.960, CI = 0.937-0.984, P IVW = 0.0010) with a lower risk of juvenile myoclonic epilepsy were identified after multiple-testing correction. Our sensitivity analysis revealed no evidence of pleiotropy, reverse causality, weak instrument bias, or heterogeneity. Conclusion: This is the first MR analysis to explore the potential causal relationship among the gut microbiota, metabolites, and epilepsy. Four gut microbiota features (two class levels, one order level, and one family level) were identified as potential interventional targets for patients with childhood absence epilepsy, generalized epilepsy with tonic-clonic seizures, and juvenile myoclonic epilepsy. Previous associations in numerous observational studies may had been interfered by confounders. More rigorous studies were needed to ascertain the relationship among the gut microbiota, metabolites, and epilepsy.

Extracellular signal-regulated kinase-dependent phosphorylation of histone H3 serine 10 is involved in the pathogenesis of traumatic brain injury.

Traumatic brain injury (TBI) induces a series of epigenetic changes in brain tissue, among which histone modifications are associated with the deterioration of TBI. In this study, we explored the role of histone H3 modifications in a weight-drop model of TBI in rats. Screening for various histone modifications, immunoblot analyses revealed that the phosphorylation of histone H3 serine 10 (p-H3S10) was significantly upregulated after TBI in the brain tissue surrounding the injury site. A similar posttraumatic regulation was observed for phosphorylated extracellular signal-regulated kinase (p-ERK), which is known to phosphorylate H3S10. In support of the hypothesis that ERK-mediated phosphorylation of H3S10 contributes to TBI pathogenesis, double immunofluorescence staining of brain sections showed high levels and colocalization of p-H3S10 and p-ERK predominantly in neurons surrounding the injury site. To test the hypothesis that inhibition of ERK-H3S10 signaling ameliorates TBI pathogenesis, the mitogen-activated protein kinase-extracellular signal-regulated kinase kinase (MEK) 1/2 inhibitor U0126, which inhibits ERK phosphorylation, was administered into the right lateral ventricle of TBI male and female rats via intracerebroventricular cannulation for 7 days post trauma. U0126 administration indeed prevented H3S10 phosphorylation and improved motor function recovery and cognitive function compared to vehicle treatment. In agreement with our findings in the rat model of TBI, immunoblot and double immunofluorescence analyses of brain tissue specimens from patients with TBI demonstrated high levels and colocalization of p-H3S10 and p-ERK as compared to control specimens from non-injured individuals. In conclusion, our findings indicate that phosphorylation-dependent activation of ERK-H3S10 signaling participates in the pathogenesis of TBI and can be targeted by pharmacological approaches.

Synthesis of ginsenoside Rb1-imprinted magnetic polymer nanoparticles for the extraction and cellular delivery of therapeutic ginsenosides.

Background: Panax ginseng (ginseng) is a traditional medicine that is reported to have cardioprotective effects; ginsenosides are the major bioactive compounds in the ginseng root. Methods: Magnetic molecularly imprinted polymer (MMIP) nanoparticles might be useful for both the extraction of the targeted (imprinted) molecules, and for the delivery of those molecules to cells. In this work, plant growth regulators were used to enhance the adventitious rooting of ginseng root callus; imprinted polymeric particles were synthesized for the extraction of ginsenoside Rb1 from root extracts, and then employed for subsequent particle-mediated delivery to cardiomyocytes to mitigate hypoxia/reoxygenation injury. Results: These synthesized composite nanoparticles were first characterized by their specific surface area, adsorption capacity, and magnetization, and then used for the extraction of ginsenoside Rb1 from a crude extract of ginseng roots. The ginsenoside-loaded MMIPs were then shown to have protective effects on mitochondrial membrane potential and cellular viability for H9c2 cells treated with CoCl2 to mimic hypoxia injury. The protective effect of the ginsenosides was assessed by staining with JC-1 dye to monitor the mitochondrial membrane potential. Conclusion: MMIPs can play a dual role in both the extraction and cellular delivery of therapeutic ginsenosides.

Integrated Analysis of Expression Profile and Potential Pathogenic Mechanism of Temporal Lobe Epilepsy With Hippocampal Sclerosis.

Objective: To investigate the potential pathogenic mechanism of temporal lobe epilepsy with hippocampal sclerosis (TLE+HS) by analyzing the expression profiles of microRNA/ mRNA/ lncRNA/ DNA methylation in brain tissues. Methods: Brain tissues of six patients with TLE+HS and nine of normal temporal or parietal cortices (NTP) of patients undergoing internal decompression for traumatic brain injury (TBI) were collected. The total RNA was dephosphorylated, labeled, and hybridized to the Agilent Human miRNA Microarray, Release 19.0, 8 × 60K. The cDNA was labeled and hybridized to the Agilent LncRNA+mRNA Human Gene Expression Microarray V3.0,4 × 180K. For methylation detection, the DNA was labeled and hybridized to the Illumina 450K Infinium Methylation BeadChip. The raw data was extracted from hybridized images using Agilent Feature Extraction, and quantile normalization was performed using the Agilent GeneSpring. P-value < 0.05 and absolute fold change >2 were considered the threshold of differential expression data. Data analyses were performed using R and Bioconductor. BrainSpan database was used to screen for signatures that were not differentially expressed in normal human hippocampus and cortex (data from BrainSpan), but differentially expressed in TLE+HS' hippocampus and NTP' cortex (data from our cohort). The strategy "Guilt by association" was used to predict the prospective roles of each important hub mRNA, miRNA, or lncRNA. Results: A significantly negative correlation (r < -0.5) was found between 116 pairs of microRNA/mRNA, differentially expressed in six patients with TLE+HS and nine of NTP. We examined this regulation network's intersection with target gene prediction results and built a lncRNA-microRNA-Gene regulatory network with structural, and functional significance. Meanwhile, we found that the disorder of FGFR3, hsa-miR-486-5p, and lnc-KCNH5-1 plays a key vital role in developing TLE+HS.

Identification of a Novel Heterozygous Mutation in the EIF2B4 Gene Associated With Vanishing White Matter Disease.

Vanishing white matter disease (VWM) is one of the most common childhood inherited leukoencephalopathies with autosomal recessive inheritance. Mutations in five genes, EIF2B1-5, have been identified as the major cause of VWM. In this study, a targeted gene capture sequencing panel comprising 160 known pathogenic genes associated with leukoencephalopathies was performed in a large Han Chinese family affected by adult-onset VWM, and a novel heterozygous missense mutation (c.1337G > A [p. R446H]) in EIF2B4 (NM_001034116.2) was detected. Further functional studies in HEK 293 cells showed dramatically reduced EIF2Bδ protein levels in the mutated group compared with the wild-type group. This study revealed that a heterozygous missense mutation (c.1337G > A [p. R446H]) in EIF2B4 was potentially associated with the adult-onset mild phenotype of VWM. In contrast to previous reports, autosomal dominant inheritance was also observed in adult-onset VWM.

Integrative analysis of expression profile indicates the ECM receptor and LTP dysfunction in the glioma-related epilepsy.

BACKGROUND: Seizures are a common symptom in glioma patients, and they can cause brain dysfunction. However, the mechanism by which glioma-related epilepsy (GRE) causes alterations in brain networks remains elusive. OBJECTIVE: To investigate the potential pathogenic mechanism of GRE by analyzing the dynamic expression profiles of microRNA/ mRNA/ lncRNA in brain tissues of glioma patients. METHODS: Brain tissues of 16 patients with GRE and 9 patients with glioma without epilepsy (GNE) were collected. The total RNA was dephosphorylated, labeled, and hybridized to the Agilent Human miRNA Microarray, Release 19.0, 8 × 60 K. The cDNA was labeled and hybridized to the Agilent LncRNA + mRNA Human Gene Expression Microarray V3.0, 4 × 180 K. The raw data was extracted from hybridized images using Agilent Feature Extraction, and quantile normalization was performed using the Agilent GeneSpring. P-value < 0.05 and absolute fold change > 2 were considered the threshold of differential expression data. Data analyses were performed using R and Bioconductor. RESULTS: We found that 3 differentially expressed miRNAs (miR-10a-5p, miR-10b-5p, miR-629-3p), 6 differentially expressed lncRNAs (TTN-AS1, LINC00641, SNHG14, LINC00894, SNHG1, OIP5-AS1), and 49 differentially expressed mRNAs play a vitally critical role in developing GRE. The expression of GABARAPL1, GRAMD1B, and IQSEC3 were validated more than twofold higher in the GRE group than in the GNE group in the validation cohort. Pathways including ECM receptor interaction and long-term potentiation (LTP) may contribute to the disease's progression. Meanwhile, We built a lncRNA-microRNA-Gene regulatory network with structural and functional significance. CONCLUSION: These findings can offer a fresh perspective on GRE-induced brain network changes.

Imaging Genetics in Epilepsy: Current Knowledge and New Perspectives.

Epilepsy is a neurological network disease with genetics playing a much greater role than was previously appreciated. Unfortunately, the relationship between genetic basis and imaging phenotype is by no means simple. Imaging genetics integrates multidimensional datasets within a unified framework, providing a unique opportunity to pursue a global vision for epilepsy. This review delineates the current knowledge of underlying genetic mechanisms for brain networks in different epilepsy syndromes, particularly from a neural developmental perspective. Further, endophenotypes and their potential value are discussed. Finally, we highlight current challenges and provide perspectives for the future development of imaging genetics in epilepsy.

Expansion of Clinical and Genetic Spectrum of DDX3X Neurodevelopmental Disorder in 23 Chinese Patients.

Aim: De novo DDX3X variants account for 1-3% of unexplained intellectual disability cases in females and very rarely in males. Yet, the clinical and genetic features of DDX3X neurodevelopmental disorder in the Chinese cohort have not been characterized. Method: A total of 23 Chinese patients (i.e., 22 female and 1 male) with 22 de novo DDX3X deleterious variants were detected among 2,317 probands with unexplained intellectual disability (ID) undertaking whole exome sequencing (WES). The age, sex, genetic data, feeding situation, growth, developmental conditions, and auxiliary examinations of the cohort were collected. The Chinese version of the Gesell Development Diagnosis Scale (GDDS-C) was used to evaluate neurodevelopment of DDX3X patients. The Social Communication Questionnaire (SCQ)-Lifetime version was applied as a primary screener to assess risk for autism spectrum disorder (ASD). Result: A total of 17 DDX3X variants were novel and 22 were de novo. Missense variants overall were only slightly more common than loss-of-function variants and were mainly located in two functional subdomains. The average age of this cohort was 2.67 (±1.42) years old. The overlapping phenotypic spectrum between this cohort and previously described reports includes intellectual disability (23/23, 100%) with varying degrees of severity, muscle tone abnormalities (17/23, 73.9%), feeding difficulties (13/23, 56.5%), ophthalmologic problems (11/23, 47.8%), and seizures (6/23, 26.1%). A total of 15 individuals had notable brain anatomical disruption (15/23, 65.2%), including lateral ventricle enlargement, corpus callosum abnormalities, and delayed myelination. Furthermore, 9 patients showed abnormal electroencephalogram results (9/23, 39.1%). Hypothyroidism was first noted as a novel clinical feature (6/23, 26.1%). The five primary neurodevelopmental domains of GDDS-C in 21 patients were impaired severely, and 13 individuals were above the "at-risk" threshold for ASD. Interpretation: Although a certain degree of phenotypic overlap with previously reported cohorts, our study described the phenotypic and variation spectrum of 23 additional individuals carrying DDX3X variants in the Chinese population, adding hypothyroidism as a novel finding. We confirmed the importance of DDX3X as a pathogenic gene in unexplained intellectual disability, supporting the necessity of the application of WES in patients with unexplained intellectual disability.

Migration characteristics as a prognostic factor in cerebral sparganosis.

OBJECTIVE: To differentiate diagnostic and prognostic factors from the clinical material of patients with cerebral sparganosis in central South China. METHODS: Consecutive patients with cerebral sparganosis from our hospital between 2010 and 2018 were retrospectively enrolled. The clinical manifestations, radiographic features, treatment, and outcomes of these patients were analyzed. RESULTS: Thirty patients with cerebral sparganosis were included, and foci migration on magnetic resonance imaging was detected in 22 patients, from whom we observed 4 migration modes: interlobar migration (50.0%, 11/22); transmidline migration (27.3%, 6/22); transventricular migration (13.6%, 3/22); and cerebellum-brainstem migration (9.1%, 2/22). The percentage of good outcomes was higher in patients with live worm capture than in those without live worm capture (75.0%, 12/16 vs 33.3%, 2/6). Exposure to preoperative antiparasitic medication was associated with worm migration toward the cortical surface, which led to a higher probability of live worm capture. CONCLUSIONS: We propose 4 modes of sparganosis migration that are correlated with worm capture and neurologic prognosis. We found that exposure to antiparasitic medication was associated with worm migration toward the cortical surface, leading to a higher probability of live worm capture. These observations suggest a novel significance for preoperative medication of cerebral sparganosis.

Efficacy and safety of vagus nerve stimulation in the treatment of refractory epilepsy. / è¿·èµ°ç¥žç»åˆºæ¿€æœ¯æ²»ç–—éš¾æ²»æ€§ç™«ç—«çš„ç–—æ•ˆå’Œå®‰å ¨æ€§.

OBJECTIVES: Vagus nerve stimulation (VNS) is a neuromodulative therapeutic technique for patients with drug-resistant epilepsy who are not suitable for resection or who have experienced a failed resection. This study aims to explore the efficacy and safety of VNS in patients with refractory epilepsy, and to analyze the influential factors for the efficacy. METHODS: A retrospective review of clinical data were conducted for 35 patients, who were treated for refractory epilepsy through VNS surgery in the Department of Neurosurgery, Xiangya Hospital, Central South University from April 2016 to August 2019. All patients were analyzed in terms of the clinical and follow-up data. RESULTS: After a mean follow-up of 26 months (6-47 months), outcome was as follows: 7 patients were MuHugh class I, 13 patients were MuHugh class II, 8 patients were MuHugh class III, and 7 patients were MuHugh class IV-V. The total efficacy rate in the short duration group was significantly higher than that in the long duration group (77.8% vs 50.0%, P=0.013), whereas different ages (P=0.382), gender (P=0.824), types of seizure (P=0.829), and MRI features (P=0.791) showed no correlation with efficacy. None patients developed permanent complication postoperatively. CONCLUSIONS: VNS is a safe and effective option in treating patients with refractory epilepsy, especially for those with short duration.

Lesionectomy for cerebral sparganosis and concomitant epilepsy: A case series of 15 patients.

OBJECTIVE: To report the clinical characteristics and surgical outcomes of patients with cerebral sparganosis and concomitant epilepsy. METHODS: We retrospectively collected the clinical data of all patients with cerebral sparganosis and concomitant epilepsy who underwent lesionectomy as treatment at Xiangya Hospital, Central South University between January 2015 and August 2019. Seizure outcomes were evaluated according to the International League Against Epilepsy (ILAE) classification. ILAE classes 1 and 2 were defined as favorable seizure outcomes, whereas ILAE classes 3-6 were defined as unfavorable seizure outcomes. RESULTS: Fifteen patients with cerebral sparganosis and concomitant epilepsy who underwent lesionectomy as treatment met the inclusion criteria. Live worms were surgical removed in 80 % of patients. With a mean follow-up of 2.4 ± 1.1 years, 66.7 % of patients demonstrated favorable seizure outcomes, with improvement of symptoms other than seizures. Longer seizure duration associated with unfavorable seizure outcomes. CONCLUSIONS: Lesionectomy is an effective treatment for patients with cerebral sparganosis and concomitant epilepsy. Early surgical treatment may offer more benefits to such patients.

UAP1L1 plays an oncogene-like role in glioma through promoting proliferation and inhibiting apoptosis.

BACKGROUND: Uridine diphosphate-N-acetylglucosamine pyrophosphorylase-1-like-1 (UAP1L1) is involved in protein glycosylation and promotes proliferation in some tumors. By analyzing the publicly available Gene Expression Omnibus (GEO) database, we found that UAP1L1 displayed a significant change between paired glioma and normal brain tissues. The purpose of this study was to investigate the expression and functional role of UAP1L1 in glioma. METHODS: To determine the expression level of UAP1L1 in glioma, immunohistochemistry (IHC) staining was performed in tissue microarrays of 160 gliomas and 24 normal brain tissues. The correlation between UAP1L1 expression and the outcomes of glioma patients was analyzed. Human glioblastoma cell lines, U251 and U87, were employed in this study. Endogenous UAP1L1 expression in U251 and U87 cells was detected by quantitative real-time polymerase chain reaction (qRT-PCR). A lentiviral short hairpin RNA (shRNA) vector (shUAP1L1) was constructed and used to infect U251 and U87 cells to knock down the expression of UAP1L1. We performed 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony formation assay, flow cytometry, human apoptosis antibody array, and in vivo subcutaneous xenograft model to investigate the biological functions of UAP1L1. RESULTS: We revealed that UAP1L1 expression was obviously upregulated in the glioma tissues. The increased UAP1L1 expression level was clinically associated with higher tumor grades and poorer patient prognoses. Moreover, we demonstrated that UAP1L1 knockdown suppressed proliferation and increased apoptosis of glioma cells in vitro. In the xenograft mouse model, we further verified that UAP1L1 knockdown could attenuate the growth of glioma cells in vivo. CONCLUSIONS: These results indicated that UAP1L1 may play an oncogene-like role in glioma, especially in high grade glioma, and thus may be of clinical importance as a future therapeutic target.

miR-135a-5p inhibitor protects glial cells against apoptosis via targeting SIRT1 in epilepsy.

Epilepsy is a common neurological disease that can induce severe physiological brain damage, including nerve cell apoptosis. MicroRNAs (miRs) have been widely investigated in epilepsy therapy. miR-135a-5p expression levels in children with temporal lobe epilepsy were found to be significantly increased. However, whether miR-135a-5p participates in epilepsy-induced cell apoptosis is not completely understood. In the present study, an in vitro model of epilepsy in BV2 microglia cells was induced using 6-µm kainic acid (KA). Reverse-transcription quantitative PCR was performed to analyze miR-135a-5p and sirtuin 1 (SIRT1) mRNA expression levels. Western blotting was performed to measure SIRT1 protein expression levels. BV2 cell proliferation and apoptosis were assessed by performing MTT assays and flow cytometry, respectively. A BCA protein assay kit was used to detect caspase-3 and caspase-9 activities. TargetScan and dual luciferase reporter assays were performed to investigate the interaction between miR-135a-5p and the 3'-untranslated region (UTR) of SIRT1. miR-135a-5p expression was significantly increased in the KA-induced in vitro model of epilepsy in BV2 microglia. miR-135a-5p inhibitor effectively promoted BV2 microglia proliferation and inhibited microglia apoptosis, whereas small interfering RNA targeting SIRT1 significantly repressed BV2 microglia proliferation and induced microglia apoptosis. In addition, the results demonstrated that the 3'-UTR of SIRT1 mRNA was targeted by miR-135a-5p, and SIRT1 knockdown attenuated miR-135a-5p inhibitor-mediated effects on epilepsy. In summary, the results of the present study identified the role of miR-135a-5p inhibitor pretreatment in protecting nerve cells against epilepsy-induced apoptosis and provided a novel strategy for the treatment of neural damage in seizures.

Factors associated with prognosis of dysembryoplastic neuroepithelial tumors patients after surgical resection: a retrospective observational study.

OBJECTIVE: To explore factors that might be associated with prognosis of dysembryoplastic neuroepithelial tumors (DNTs). METHODS: DNTs patients who were admitted to the Department of Neurosurgery of Xiangya Hospital between 1 January 2010 and 31 December 2018 and underwent surgical resection were retrospectively analyzed. Clinical, neuroimaging, and pathological features of DNTs were compared among patients with different outcomes and analyzed using the Kaplan-Meier curves and univariable Cox regression analysis. RESULTS: Thirty-three DNTs patients were included finally, of which the average age at seizure onset was 11.59 ± 7.46 years old and the average duration of seizures prior to surgical resection was 3.00 ± 4.68 years. After surgical resection, the patients were followed up for 2.39 ± 1.97 years, and 28 patients (84.85%) were seizure-free (class I of the Engel Outcome Scale) while five patients (15.15%) were seizure-continuous (class II or III of the Engel Outcome Scale). When compared with seizure-free patients, seizure-continuous patients had greater age at seizure onset and longer duration of seizures before surgical resection (p < .05). No variables were found to be statistically significantly associated with prognosis in univariable Cox regression analysis, but patients with extra-temporal DNTs were found to have better prognosis than those with temporal DNTs (log-rank test p = .048). CONCLUSIONS: Elder seizure onset age, longer duration of seizures prior to surgical resection, and a temporal location may be risk factors of poor prognosis for DNTs patients after surgical resection.

The Role of Hippocampal Neurogenesis in ANT-DBS for LiCl-Pilocarpine-Induced Epileptic Rats.

PURPOSE: Abnormal neurogenesis in the hippocampus after status epilepticus (SE) has been suggested as a key pathogeny of temporal lobe epilepsy. This study aimed to investigate the effect of deep brain stimulation of the anterior thalamic nucleus (ANT-DBS) on hippocampal neurogenesis in LiCl-pilocarpine-induced epileptic rats and to analyze its relationship with postoperative spontaneous recurrent seizures (SRS) and anxiety. METHOD: SE was induced by a systemic LiCl-pilocarpine injection in adult male rats. Rats in the DBS group underwent ANT-DBS immediately after successful SE induction. SRS was only recorded during the chronic stage. An elevated plus maze was used to evaluate the level of anxiety in rats 7, 28, and 60 days after SE onset. After the elevated plus-maze experiment, rats were sacrificed under anesthesia in order to evaluate hippocampal neurogenesis. Doublecortin (DCX) was used as a marker for neurogenesis. RESULTS: During the chronic stage, SRS in rats in the DBS group were significantly decreased. The level of anxiety was increased significantly in rats in the DBS group 28 days after SE, while no significant differences in anxiety levels were found 7 and 60 days after SE. The number of DCX-positive cells in the hippocampus was significantly increased 7 days after SE and was significantly decreased 60 days after SE in all rats in which SE was induced. However, the number of DCX-positive cells in the DBS group was significantly lower than that in the other groups 28 days after SE. CONCLUSIONS: ANT-DBS may suppress SRS and increase the postoperative anxiety of epileptic rats by influencing hippocampal neurogenesis.