Neuroreport最新文献

Epilepsy and migraine without aura (MWoA) are often comorbid, but the exact mechanisms are unclear. Magnetic resonance spectroscopy (1H-MRS) may help to understand the neurometabolic mechanisms in patients with epilepsy comorbid with MWoA (EWM). In this prospective cross-sectional study, we recruited 64 female patients, including 24 with EWM, 20 with epilepsy, and 20 with MWoA, as well as 20 age-level-matched and educational-level-matched female healthy controls from our hospital between August 2021 and November 2022. A single-voxel point-resolved spectroscopy sequence was used to acquire spectra of the bilateral dorsolateral prefrontal cortices (DLPFCs). Metabolites were quantified by linear combination model software, and the values were corrected for the partial volume effect of cerebrospinal fluid. MRS data comparisons were performed with multivariate analyses of variance. Correlation analyses were calculated between metabolites and main clinical data. The results showed that N-acetyl aspartate (NAA) was asymmetrical between the bilateral DLPFCs. Both NAA and myoinositol were significantly reduced in EWM than in healthy controls. Choline-containing compounds (Cho) were higher in MWoA than in the other three groups. Correlation analyses revealed that NAA of the right DLPFC and Cho of the bilateral DLPFCs in EWM were negatively related to migraine frequency. In addition, glutamate and glutamine (Glu and Gln, Glx) of the right DLPFC in EWM were negatively correlated with migraine severity. Our findings suggested that comorbid epilepsy and MWoA in female patients can lead to a synergistic reduction of both NAA and myoinositol, reflecting more serious injuries of neurons and glial cells.

Seizure waves of epilepsy can propagate in a coupled thalamocortical model, which typically occurs in malfunctioning neuronal networks. However, it remains unclear whether thalamic feed-forward inhibition (FFI) and feed-back inhibition (FBI), the two most important microcircuits in this network, have propagation effects. In this study, we first investigated the importance of the pyramidal neuronal population-thalamic reticular nucleus and specific relay nucleus-thalamic reticular nucleus pathways in the Taylor model for seizure control as FFI and FBI, respectively. Subsequently, using the FBI as a crucial parameter, we constructed 2- and 3-compartment coupling models and evaluated their impact on seizure propagation in other chambers by varying the degree of coupling strength. Finally, we replicated the above study in a 10-compartment model to ensure the robustness of the findings. We confirmed that FBI is more effective by analyzing the combined effect of FFI and FBI, and the pathology state does advance as the coupling strength is increased. These findings elucidate the roles that these two pathways play in the propagation of epileptic seizures and may offer fresh perspectives on the clinical management of epilepsy.

Mounting neuroimaging evidence indicates that patients with thyroid-associated ophthalmopathy (TAO) demonstrate altered brain function and structure. Nonetheless, the alterations in the topological properties of the functional brain connectome in TAO patients are not yet fully understood. This study aimed to investigate the topological organization of the functional brain connectome in TAO patients using graph-theoretic methods. Twenty-five TAO patients (10 males and 15 females) and 25 age-, sex-, and education-matched healthy controls (HCs) (10 males and 15 females) (the TAO and HC data are from the same dataset in previous studies) underwent resting-state MRI scans. Graph-theoretic analysis was used to study the global, nodal, and edge topological properties of the brain's functional connectome. Both the TAO and HC groups exhibited high-efficiency small-world networks in their brain functional networks. However, there were no significant differences in small-world properties (Cp, γ, λ, Lp, and σ) and network efficiency [global and local efficiencies (Eloc)] between the two groups. In addition, the TAO group demonstrated reduced betweenness centrality in the right fusiform and increased nodal Eloc in the right intraparietal sulcus ( P  < 0.05, Bonferroni-corrected). Furthermore, the TAO group displayed altered functional connections among the default-mode network (DMN), visual network (VN), sensorimotor network (SMN), and cingulo-opercular network (CON). Patients with TAO exhibited abnormal topological organization of the human brain connectome, including decreased betweenness centrality and increased nodal Eloc. Moreover, the TAO group displayed altered functional connections primarily within the DMN, VN, SMN, and CON. These findings provide crucial insights into the neural mechanisms underlying visual loss, abnormal emotion regulation, and cognitive deficits in TAO patients.

Depression in male and female are commonly associated with different prevalence, severity, and, in some cases, distinct syndromes or subtypes. However, only a small amount of research has been conducted to completely understand the underlying neuroanatomical mechanisms. The goal of the current study was to provide neural markers for specific depression therapies by demonstrating the differences in aberrant prefrontal activity between male and female depressed subjects during an emotional autobiographical memory test. The study included 127 young adults who were randomly assigned to one of two groups: male depression (62 participants) or female depression (65 participants). The average oxyhemoglobin levels in the dorsolateral prefrontal cortex throughout the emotional autobiographical memory task were assessed utilizing 53-channel functional near-infrared spectroscopy imaging equipment. The oxy-Hb activation in the left dorsolateral prefrontal cortex (lDLPFC) and right dorsolateral prefrontal cortex (rDLPFC) had no significant interaction between groups and emotional valences. A significant main effect was found between male and female, with female depression groups showing lower oxy-Hb activity in lDLPFC and rDLPFC than male depression groups. Male and female depression patients showed distinct brain activation in the DLPFC during an emotional autobiographical memory test, suggesting potential specific neurological indicators for varied somatic symptoms in male and female depression patients. These distinctions should be taken into account while creating preventive measures.

Sepsis-associated encephalopathy (SAE) is a severe complication of sepsis. Reduced glutathione (GSH) has antioxidant properties and is used as a neuroprotective agent in some studies. However, research on the application of exogenous GSH in the treatment of SAE is limited. This study aimed to determine the effects of exogenous GSH in pediatric SAE patients and mice. We evaluated clinical parameters, inflammatory factors, and oxidative stress before and after GSH treatment. The clinical trials demonstrated that GSH treatment improved brain damage markers (S-100 beta protein, brain fatty acid-binding protein), increased neurological status scores (Glasgow coma scale), and reduced Pediatric Risk of Mortality III scores in children with SAE. GSH treatment also significantly reduced the levels of inflammatory factors (interleukin-6, tumor necrosis factor-α) and decreased lipid peroxidation (superoxide dismutase). Additionally, GSH reduced lipid peroxidation resulting from abnormal lipid metabolism, as indicated by the levels of acyl-CoA synthetase long-chain family member 4, lysophosphatidylcholine acyltransferase 3, and glutathione peroxidase 4. In-vivo experiments showed that the neuroprotective effect of GSH was dose-dependent, with better effects observed at medium and high doses. Furthermore, GSH alleviated brain damage, suppressed the release of inflammatory factors, and inhibited lipid peroxidation in SAE mice. The animal experiments also showed that GSH reduces lipid peroxidation through the 15-lipoxygenase/phosphatidylethanolamine binding protein 1/glutathione peroxidase 4 pathway. Our study suggests that exogenous GSH has neuroprotective effects in pediatric SAE. These findings provide a basis for the potential use of GSH as a therapeutic method for SAE.

This project is conceived to reveal the role of lidocaine in the process of Alzheimer's disease (AD) and its possible downstream targets. After the employment of AD cell model in mice hippocampal neuronal HT-22 cells in the presence of amyloid-β1-42 (Aβ1-42), Cell Counting Kit-8 method investigated cell viability. Oxidative damage was assayed based on a dichloro-dihydro-fluorescein diacetate fluorescent probe and commercially available kits. The 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolocarbocyanine iodide fluorescent probe estimated mitochondrial function. Terminal-deoxynucleotidyl transferase mediated nick end labeling, western blotting, and immunofluorescence appraised the apoptotic level. Western blot also ascertained the alternations of nerve growth factors (NGF)-protein kinase B (Akt) pathway-related proteins. Aβ1-42 concentration dependently triggered the viability loss, oxidative damage, and apoptosis in HT-22 cells. Lidocaine promoted the viability and reduced the mitochondrial impairment and mitochondria-dependent apoptosis in Aβ1-42-treated HT-22 cells in a concentration-dependent manner. Besides, lidocaine activated the NGF-Akt pathway and NGF absence blocked NGF-Akt pathway, aggravated mitochondrial dysfunction as well as mitochondria-dependent apoptosis in lidocaine-administrated HT-22 cells in response to Aβ1-42. Altogether, these observations concluded that lidocaine might stimulate NGF-Akt pathway to confer protection against mitochondrial impairment and apoptosis in Aβ1-42-mediated cellular model of AD.

Long-term hypothermia has been reported to prevent intracranial pressure (ICP) rebound in clinical patients, but the duration for hypothermia and the corresponding ICP data are not available. This study investigated the optimal duration of long-term hypothermia in traumatic brain injury (TBI) rats, and observed the effect on ICP and neurological function. In this study, we established a rat severe TBI model with electronic Controlled Cortical Injury device, and implemented hypothermia (33 °C) for different durations. The motor function of the rats in each group was evaluated by beam walking test and inclined-grid climbing test, brain water content was calculated by the wet-dry weight method, Evan's blue staining was used to measure the blood-brain barrier (BBB) permeability, the change of hippocampal neurons was observed by Nissl staining, the expressions of BrdU, NeuN, and CD86 positive cells were detected by immunofluorescence staining, and the expressions of Bcl-2, Bax, iNOS, IL-10, and Arg-1 were detected by Western blot. We found that therapeutic hypothermia improved neurological recovery after TBI with declining ICP, reducing brain edema, decreasing BBB permeability, promoting neurogenesis, inhibiting apoptosis, and regulating inflammation. Moreover, 48 h hypothermia amplified the neuroprotective effect after injury on the basis of 4 or 24 h hypothermic treatment. Both 4 and 24 h hypothermia led to ICP rebound during or after rewarming, whereas 48 h hypothermia completely abolished ICP rebound. Our study suggests that long-term hypothermia amplifies neuroprotection after TBI by antagonizing ICP rebound.

The objective is to investigate the effects of apelin-13 in models of post-traumatic stress disorder (PTSD). Mature male CD1 mice were subjected to the single prolonged stress method to induce PTSD-related behaviors. These behaviors were then evaluated using the elevated plus maze test, Morris water maze test, and open field test. Hippocampal neural cell death was assessed using propidium iodide labeling. The expression of hippocampal autophagy pathway-associated proteins was determined through immunoblotting analysis, and LC3 levels were also measured via quantitative real-time reverse transcription-PCR. The results demonstrate that administration of apelin-13 suppressed PTSD-induced hippocampal neural cell death and alleviated PTSD-related behaviors in mice. Additionally, PTSD led to an up-regulation of LC3 and FoxO3a, and down-regulation of P62, p-PI3K, p-Akt, and p-FoxO3a in the hippocampus. However, these changes were reversed by apelin-13 treatment. These findings support the hypothesis that apelin-13 prevents the development of PTSD-like behavior and inhibits autophagy of neuronal cells in a mouse model of PTSD. Apelin-13 may hold potential as a therapeutic agent for PTSD in clinical applications.

The objective of this study is to explore whether sodium valproate (VPA) alleviates epileptic seizures via suppressing lysyl oxidase (Lox)-mediated ferroptosis. Epileptic seizure mouse model was prepared via intrahippocampal injection of kainic acid (250 ng/μl). After treatment with kainic acid, VPA was injected intraperitoneally by the dose of 250 mg/kg twice daily for 4 days. Ferroptosis-associated indices including lipid peroxides (LPO) level and Ptgs2 mRNA in hippocampal tissue samples were detected. Additionally, effects of VPA on Lox mRNA and enzymatic activity were assessed by quantitative real-time PCR and a commercial kit, respectively. Neuronal survival was assessed by Nissl staining. In kainic acid-induced epileptic seizure mouse model, VPA significantly suppressed LPO level and Ptgs2 mRNA and the suppression of ferroptosis was positively correlated with its anti-seizure effect. Lox mRNA and enzymatic activity were also found to decrease in hippocampus of epileptic seizure mice after VPA treatment. Furthermore, overexpression of Lox via adeno-associated virus infection remarkably abrogated the inhibitory effect of VPA on ferroptosis and neuronal impairment together with its anti-seizure effect. VPA suppresses Lox-mediated ferroptosis process, which can provide the explanation for its anti-seizure property.

Our study aims to explore the differences in functional connectivity in the nucleus accumbens (NAc) between patients with melancholic depression and non-melancholic depression (NMD) and their relation to melancholic depression's pathogenesis. We recruited 60 melancholic depression, 58 NMD, and 80 healthy controls, all matched for gender, age, and education. Functional connectivity analysis focused on bilateral NAc as the region of interest, comparing it with the whole brain and correlating significant differences with clinical scores. Melancholic depression patients showed reduced functional connectivity between the left NAc and anterior brain regions, and between the right NAc and temporal and frontal areas, compared to healthy controls. In contrast, NMD patients displayed reduced functional connectivity only between the left NAc and the posterior cingulate cortex. Melancholic depression patients also exhibited increased functional connectivity between the right NAc and the middle frontal gyrus, unlike NMD patients. The findings suggest that melancholic depression patients exhibit unique NAc functional connectivity patterns, particularly with the default mode network and prefrontal areas, suggesting atypical reward-circuitry interactions. The right NAc's connection to the prefrontal gyrus may distinguish melancholic depression from NMD.