Interference of Interleukin-1ß Mediated by Lentivirus Promotes Functional Recovery of Spinal Cord Contusion Injury in Rats via the PI3K/AKT1 Signaling Pathway.

Purpose: Inflammation and apoptosis after spinal cord contusion (SCC) are important causes of irreversible spinal cord injury. Interleukin-1ß (IL-1ß) is a key inflammatory factor that promotes the aggravation of spinal cord contusion. However, the specific role and regulatory mechanism of IL-1ß in spinal cord contusion is still unclear. Therefore, this study applied bioinformatics to analyze and mine potential gene targets interlinked with IL-1ß, animal experiments and lentiviral interference technology were used to explore whether IL-1ß affected the recovery of motor function in spinal cord contusion by interfering with PI3K/AKT1 signaling pathway. Method: This study used bioinformatics to screen and analyze gene targets related to IL-1ß. The rat SCC animal model was established by the Allen method, and the Basso Beattie Bresnahan (BBB) score was used to evaluate the motor function of the spinal cord-injured rats. Immunohistochemistry and immunofluorescence were used to localize the expression of IL-1ß and AKT1 proteins in spinal cord tissue. Quantitative polymerase chain reaction and Western blot were used to detect the gene and protein expressions of IL-1ß, PI3K, and AKT1. RNAi technology was used to construct lentivirus to inhibit the expression of IL-1ß, lentiviral interference with IL-1ß was used to investigate the effect of IL-1ß and AKT1 on the function of spinal cord contusion and the relationship among IL-1ß, AKT1, and downstream signaling pathways. Results: Bioinformatics analysis suggested a close relationship between IL-1ß and AKT1. Animal experiments have confirmed that IL-1ß is closely related to the functional recovery of spinal cord contusion. Firstly, from the phenomenological level, the BBB score decreased after SCC, IL-1ß and AKT1 were located in the cytoplasm of neurons in the anterior horn of the spinal cord, and the expression levels of IL-1ß gene and protein in the experimental group were higher than those in the sham operation group. At the same time, the expression of AKT1 gene decreased, the results suggested that the increase of IL-1ß affected the functional recovery of spinal cord contusion. Secondly, from the functional level, after inhibiting the expression of IL-1ß with a lentivirus-mediated method, the BBB score was significantly increased, and the motor function of the spinal cord was improved. Thirdly, from the mechanistic level, bioinformatics analysis revealed the relationship between IL-1ß and AKT1. In addition, the experiment further verified that in the PI3K/AKT1 signaling pathway, inhibition of IL-1ß expression upregulated AKT1 gene expression, but PI3K expression was unchanged. Conclusion: Inhibition of IL-1ß promotes recovery of motor function after spinal cord injury in rats through upregulation of AKT1 expression in the PI3K/AKT1 signaling pathway. Bioinformatics analysis suggested that IL-1ß may affect apoptosis and regeneration by inhibiting the expression of AKT1 in the PI3K/AKT1 signaling pathway to regulate the downstream FOXO, mTOR, and GSK3 signaling pathways; thereby hindering the recovery of motor function in rats after spinal cord contusion. It provided a new perspective for clinical treatment of spinal cord contusion in the future.

COVID-19 vaccinations for patients with epilepsy in Guizhou Province, China: A cross-sectional study.

Several COVID-19 vaccines have been approved for emergency use according to China's immunization programs. These vaccines has created hope for patients with epilepsy, because the vaccines can help to reduce their risk of becoming infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The aim of this study was to investigate the COVID-19 vaccine safety in patients with epilepsy. Here, we assessed the time of symptom control and the features of adverse events of seizure patients following their COVID-19 vaccinations. The results showed that adverse events of COVID-19 vaccinations for epilepsy patients included local pain at the injection site, dizziness and headache, epileptic attack, somnolence, limb weakness, limb pain, allergy, and fever. In addition, the average recovery time of the adverse events was approximately 42 h. More importantly, our study showed that it was relatively safe to vaccinate epilepsy patients who did not experience seizures for approximately 12 months prior to the immunization date.

Rapamycin improves the survival of epilepsy model cells by blocking phosphorylation of mTOR base on computer simulations and cellular experiments.

PURPOSE: Epilepsy is a chronic brain dysfunction characterized by recurrent epileptic seizures. Rapamycin is a naturally occurring macrolide from Streptomyces hygroscopicus, and rapamycin may provide a protective effect on the nervous system by affecting mTOR. Therefore, we investigated the pharmacologic mechanism of rapamycin treating epilepsy through bioinformatics analysis, cellular experiments and supercomputer simulation. METHODS: Bioinformatics analysis was used to analyze targets of rapamycin treating epilepsy. We established epilepsy cell model by HT22 cells. RT-qPCR, WB and IF were used to verify the effects of rapamycin on mTOR at gene level and protein level. Computer simulations were used to model and evaluate the stability of rapamycin binding to mTOR protein. RESULTS: Bioinformatics indicated mTOR played an essential role in signaling pathways of cell growth and cell metabolism. Cellular experiments showed that rapamycin could promote cell survival, and rapamycin did not have an effect on mRNA expression of mTOR. However, rapamycin was able to significantly inhibit the phosphorylation of mTOR at protein level. Computer simulations indicated that rapamycin was involved in the treatment of epilepsy through regulating phosphorylation of mTOR at protein level. CONCLUSION: We found that rapamycin was capable of promoting the survival of epilepsy cells by inhibiting the phosphorylation of mTOR at protein level, and rapamycin did not have an effect on mRNA expression of mTOR. In addition to the traditional study that rapamycin affects mTORC1 complex by acting on FKBP12, this study found rapamycin could also directly block the phosphorylation of mTOR, therefore affecting the assembly of mTORC1 complex and mTOR signaling pathway.

EEG brain network variability is correlated with other pathophysiological indicators of critical patients in neurology intensive care unit.

Continuous electroencephalogram (cEEG) plays a crucial role in monitoring and postoperative evaluation of critical patients with extensive EEG abnormalities. Recently, the temporal variability of dynamic resting-state functional connectivity has emerged as a novel approach to understanding the pathophysiological mechanisms underlying diseases. However, little is known about the underlying temporal variability of functional connections in critical patients admitted to neurology intensive care unit (NICU). Furthermore, considering the emerging field of network physiology that emphasizes the integrated nature of human organisms, we hypothesize that this temporal variability in brain activity may be potentially linked to other physiological functions. Therefore, this study aimed to investigate network variability using fuzzy entropy in 24-hour dynamic resting-state networks of critical patients in NICU, with an emphasis on exploring spatial topology changes over time. Our findings revealed both atypical flexible and robust architectures in critical patients. Specifically, the former exhibited denser functional connectivity across the left frontal and left parietal lobes, while the latter showed predominantly short-range connections within anterior regions. These patterns of network variability deviating from normality may underlie the altered network integrity leading to loss of consciousness and cognitive impairment observed in these patients. Additionally, we explored changes in 24-hour network properties and found simultaneous decreases in brain efficiency, heart rate, and blood pressure between approximately 1 pm and 5 pm. Moreover, we observed a close relationship between temporal variability of resting-state network properties and other physiological indicators including heart rate as well as liver and kidney function. These findings suggest that the application of a temporal variability-based cEEG analysis method offers valuable insights into underlying pathophysiological mechanisms of critical patients in NICU, and may present novel avenues for their condition monitoring, intervention, and treatment.

Disease-specific resting-state EEG network variations in schizophrenia revealed by the contrastive machine learning.

Given a multitude of genetic and environmental factors, when investigating the variability in schizophrenia (SCZ) and the first-degree relatives (R-SCZ), latent disease-specific variation is usually hidden. To reliably investigate the mechanism underlying the brain deficits from the aspect of functional networks, we newly iterated a framework of contrastive variational autoencoders (cVAEs) applied in the contrasts among three groups, to disentangle the latent resting-state network patterns specified for the SCZ and R-SCZ. We demonstrated that the comparison in reconstructed resting-state networks among SCZ, R-SCZ, and healthy controls (HC) revealed network distortions of the inner-frontal hypoconnectivity and frontal-occipital hyperconnectivity, while the original ones illustrated no differences. And only the classification by adopting the reconstructed network metrics achieved satisfying performances, as the highest accuracy of 96.80% ± 2.87%, along with the precision of 95.05% ± 4.28%, recall of 98.18% ± 3.83%, and F1-score of 96.51% ± 2.83%, was obtained. These findings consistently verified the validity of the newly proposed framework for the contrasts among the three groups and provided related resting-state network evidence for illustrating the pathological mechanism underlying the brain deficits in SCZ, as well as facilitating the diagnosis of SCZ.

Mechanical Thrombectomy for Refractory Cerebral Venous Sinus Thrombosis in a Child with Nephrotic Syndrome : A Case Report.

Nephrotic syndrome (NS) is associated with cerebral venous sinus thrombosis (CVST), which is a rare cerebrovascular disorder in children. Systemic anticoagulation with heparin is the standard therapy for CVST, and mechanical thrombectomy (MT) has been described as a salvage treatment for adult anticoagulant refractory CVST, However, it has never been reported in children. We describe a case of MT for refractory CVST in a child with NS. A 13-year-old boy with newly diagnosed NS presented to an emergency department with acute headache. A head computed tomography showed acute thrombus in the superior sagittal sinus, straight sinus and transverse sinus. The child was started on heparin therapy, but clinically deteriorated and became unresponsive. In view of the rapid deterioration of the condition after anticoagulation treatment, the patient received intravascular treatment. Several endovascular technologies, such as stent retriever and large bore suction catheter have been adopted. After endovascular treatment, the patient's neurological condition was improved within 24 hours, and magnetic resonance venography of the head demonstrated that the CVST was reduced. The child recovered with normal neurological function at discharge. This case highlights the importance of considering MT for refractory CVST, and we suggest that MT may be considered for refractory CVST with NS in children.

DDX3X Deficiency Attenuates Pyroptosis Induced by Oxygen-glucose Deprivation/Reoxygenation in N2a Cells.

BACKGROUND: NOD like receptor protein 3 (NLRP3) inflammasome-mediated pyroptosis is strongly related to cerebral ischemia/reperfusion (I/R) injury. DDX3X, the DEAD-box family's ATPase/RNA helicase, promotes NLRP3 inflammasome activation. However, whether DDX3X deficiency attenuates NLRP3 inflammasome-mediated pyroptosis induced by cerebral I/R injury. OBJECTIVES: This study investigated whether DDX3X deficiency attenuates NLRP3 inflammasomemediated pyroptosis in N2a cells after oxygen-glucose deprivation/ reoxygenation (OGD/R) treatment. METHODS: In vitro model of cerebral I/R injury, mouse neuro2a (N2a) cells subjected to OGD/R were treated with the knockdown of DDX3X. Cell counting kit-8 (CCK-8) assay and Lactate dehydrogenase (LDH) cytotoxicity assay were conducted to measure cell viability and membrane permeability. Double immunofluorescence was performed to determine the pyroptotic cells. Transmission electron microscopy (TEM) was used to observe morphological changes of pyroptosis. Pyroptosis-associated proteins were analyzed by Western blotting. RESULTS: The OGD/R treatment reduced cell viability, increased pyroptotic cells and released LDH compared to the control group. TEM showed membrane pore formation of pyroptosis. Immunofluorescence showed that GSDMD was translocated from the cytoplasm to the membrane after OGD/R treatment. Western blotting showed that the expression of DDX3X, and pyroptosis-related proteins (NLRP3, cleaved-Caspase1, and GSDMD-N) were increased after OGD/R treatment. Nevertheless, DDX3X knockdown markedly improved cell viability and reduced LDH release, expression of pyroptosis-related proteins, and N2a cells pyroptosis. DDX3X knockdown significantly inhibited membrane pore formation and GSDMD translocation from cytoplasm to membrane. CONCLUSION: This research demonstrates for the first time that DDX3X knockdown attenuates OGD/R induced NLRP3 inflammasome activation and pyroptosis, which implies that DDX3X may become a potential therapeutic target for cerebral I/R injury.

Differentiating Between Alzheimer's Disease and Frontotemporal Dementia Based on the Resting-State Multilayer EEG Network.

Frontotemporal dementia (FTD) is frequently misdiagnosed as Alzheimer's disease (AD) due to similar clinical symptoms. In this study, we constructed frequency-based multilayer resting-state electroencephalogram (EEG) networks and extracted representative network features to improve the differentiation between AD and FTD. When compared with healthy controls (HC), AD showed primarily stronger delta-alpha cross-couplings and weaker theta-sigma cross-couplings. Notably, when comparing the AD and FTD groups, we found that the AD exhibited stronger delta-alpha and delta-beta connectivity than the FTD. Thereafter, by extracting the representative network features and then applying these features in the classification between AD and FTD, an accuracy of 81.1% was achieved. Finally, a multivariable linear regressive model was built, based on the differential topologies, and then adopted to predict the scores of the Mini-Mental State Examination (MMSE) scale. Accordingly, the predicted and actual measured scores were indeed significantly correlated with each other ( r = 0.274, p = 0.036). These findings consistently suggest that frequency-based multilayer resting-state networks can be utilized for classifying AD and FTD and have potential applications for clinical diagnosis.

The long-term effect of modulated acoustic stimulation on alteration in EEG brain network of chronic tinnitus patients: An exploratory study.

Acoustic stimulation is one of the most influential techniques for distressing tinnitus, while how it functions to reverse neural changes associated with tinnitus remains undisclosed. In this study, our objective is to investigate alterations in brain networks to shed light on the enigma of acoustic intervention for tinnitus. We designed a 75-day long-term acoustic intervention experiment, during which chronic tinnitus patients received daily modulated acoustic stimulation with each session lasting 15 days. Every 15 days, professional tinnitus assessments were conducted, collecting both electroencephalogram (EEG) and tinnitus handicap inventory (THI) data from the patients. Thereafter, we investigated the changes in EEG network organizations during continuous acoustic stimulation and their progressive evolution throughout long-term therapy, alongside exploring the associations between the evolving changes of the network alterations and THI. Our current study findings reveal reorganization in alpha/beta long-range frontal-parietal-occipital connections as well as local frontal and parietal-occipital regions induced by acoustic stimulation. Furthermore, we observed a decrease in modulation effects as therapy sessions progressed. These alterations in brain networks reflect the reversal of tinnitus-related neural activities, particularly distress and perception; thus contributing to tinnitus rehabilitation through long-term modulation effects. This study provides unique insights into how long-term acoustic intervention affects the network organizations of tinnitus patients and deepens our understanding of the pathophysiological mechanisms underlying tinnitus rehabilitation.

Prophylactic AEDs Treatment for Patients With Supratentorial Meningioma Does Not Reduce the Rate of Perioperative Seizures: A Retrospective Single-Center Cohort Study.

Meningiomas, the most common brain tumor, inevitably require surgical treatment. However, the efficacy of prophylactic antiepileptic drugs (AEDs), in reducing the frequency of new-onset seizures during the perioperative period remains controversial. To further clarify if prophylactic antiepileptic drug treatment for patients with meningioma had value, we reviewed the medical records of 186 supratentorial meningioma patients who were operated at our hospital between 2016 and 2018. SPSS 24.0 software was used for statistical analysis. The results of univariate analysis showed that factors including age, sex, the course of the disease (years), maximum cross-sectional area of the tumor, location of the tumor, multiple or single tumors, adjacent to the cortex, peritumoral brain edema, World Health Organization classification, and peritumoral adhesion were not associated with perioperative seizures (P >0.05). Furthermore, the results of multivariate analysis revealed hydrocephalus (OR 4.87 P = 0.05) and non-skull base location (OR 1.88 P = 0.04) were significant risk factors for perioperative in-hospital seizures. Prophylactic valproic acid treatment did not contribute to the alleviation of perioperative seizures (OR 1.76 P = 0.04). However, Multivariate logistic regression analyses excluding the patients with seizures before operation confirmed prophylactic valproic acid treatment did not reduce the frequency of seizures during the perioperative period (OR 1.84 P = 0.04). Taken together, the data suggest that prophylactic valproic acid treatment for patients with supratentorial meningioma does not reduce the rate of perioperative seizures.

Corrigendum: Prophylactic AEDs Treatment for Patients With Supratentorial Meningioma Does Not Reduce the Rate of Perioperative Seizures: A Retrospective Single-Center Cohort Study.

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[ERKl/2 signaling pathway mediates heme oxygenase-1 up-regulation by minocycline in PC12 cells exposed to oxygen glucose deprivation].

OBJECTIVE: To investigate the effects of minocycline in promoting the survival of pheochromocytoma (PCI2) cells exposed to oxygen glucose deprivation (OGD) and explore the underlying mechanisms. METHODS: An in vitro cell model of cerebral ischemia was established by OGD for 6 h in PCI2 cells with pretreatment with minocycline or an ERK1/2 inhibitor. At 24 h after OGD injury, the cells were evaluated for cell viability by MTT assay and expressions of heme oxygenase-I (HO-I) and phospholylated extracellular signal-regulated protein kinase 1/2 (ERK1/2) by Western blotting. RESULTS: The cell viability decreased dramatically following OGD. Pretreatment with minocycline (O.I-IO JJ.mol/L) induced a significant increase in the cell viability after OGD and caused up-regulation of HO-I protein and enhanced ERK1/2 phospholylation, and the effects were especially obvious with 1 JJ.mol/L minocycline and were abolished by inhibition of ERK1/2 activity with UOI26 (IO JJ.mol/L). CONCLUSION: Minocycline can protect PCI2 cells against OGD-induced toxicity by up-regulating HO-I protein expression through ERKl/2 signaling pathways.

A quantitative study on changes of the myelinated fibers in the cerebral cortex of cortical dysplasia rats.

An animal model of cortical dysplasia was established through X-ray irradiation induced subcortical heterotopic nodules in rats. Transmission electron microscopy detection of the ultrastructure and the stereology examination showed that there was a significant decrease in cerebral white matter and hippocampal volume, the total volume, volume density, length density and total length of the myelinated fibers in the white matter of cortical dysplasia rats. Subcortical heterotopic nodules of the hippocampal CA1 region and synaptic number density in the CA3 region were reduced compared with normal rats. Our experimental findings indicate that erosed subcortical heterotopic nodules, decreased total length of myelinated nerve fibers and demyelination directly lead to a reduction of white matter volume.