Folia neuropathologica最新文献

Age-dependent oxidative stress is considered to be involved in degenerative processes in age-related neurodegenerative disorders. The L1 cell adhesion molecule (L1CAM or L1) plays an essential role in the regeneration process following neural lesions in the adult nervous system. Protein kinase D1 (PKD1) is increasingly implicated in neuroprotection. Hence, the present study aimed to investigate the possible functional association between L1 and phosphorylated PKD1 (pPKD1) in oxidative stress-induced senescence. The study revealed that recombinant L1 (rL1) upregulated PKD1 phosphorylation, the pErk1/2 level and the Bcl2/Bax ratio in SK-N-SH cells in a concentration-dependent manner, with a peak level observed at 5 nM. L1 also increased the pPKD1 level in human pluripotent stem cells. In the 20 µM H2O2-induced senescence SK-N-SH cell model, L1 also increased the pPKD1 level and decreased the number of SA-b-gal-positive cells. On the whole, the results of the present study suggest that L1 is capable of modulating PKD1 phosphorylation to inhibit oxidative stress-induced senescence.

Introduction: The aim of the study was to investigate the clinical efficacy of Buyang Huanwu Decoction (BHD) in the treatment of patients who had an acute ischemic stroke (AIS).

Material and methods: A total of 100 patients who had experienced an AIS were selected as participants and were randomly divided into the control group and the observation group. Patients in the control group received comprehensive treatment using Western medicine, while those in the observation group received BHD internally. Both groups received ongoing treatment for 2 weeks. We examined the effects of BHD on traditional Chinese medicine (TCM) syndrome scores and neurological deficits, as well as on the expression of S100 calcium-binding protein b (S100b), neuron-specific enolase (NSE), matrix metalloproteinase-9 (MMP-9), and vascular endothelial growth factor (VEGF) in brain tissue.

Results: By monitoring patients' adverse reactions and laboratory test indicators, it was found that BHD did not significantly increase the safety risk of patients during the treatment process. The TCM evidence score and National Institutes of Health Stroke Scale (NIHSS) score of the observation group were lower compared with the control group after treatment ( p < 0.05). The TCM evidence score and NIHSS reduction of the observation group were decreased compared with those before treatment ( p < 0.05). The serum S100b protein and NSE levels in the observation group were lower than those in the control group before and after treatment ( p < 0.05). The serum MMP-9 level of the observation group was lower compared with the control group, and the serum VEGF level was higher than that of the control group after treatment ( p < 0.05). The serum MMP-9 level in the observation group was decreased and the serum VEGF level was increased compared with those before treatment ( p < 0.05). The overall response rate of the observation group was higher than that of the control group ( p < 0.05). Spearman correlation analysis revealed no correlation between TCM syndrome score and S100 protein, NSE, MMP-9, and VEGF ( p > 0.05). Furthermore, the NIHSS score was negatively correlated with MMP-9 (r s = -0.359, p < 0.05) but not with S100 protein, NSE, and VEGF ( p > 0.05).

Conclusions: BHD boasts various benefits in the treatment of AIS patients with Qi deficiency and blood stasis. The mechanism may be associated with the protection of vascular endothelial cell integrity and the promotion of endothelial cell proliferation.

The aim was to develop an artificial intelligence (AI)-based identification system using a deep learning method based on convolutional neural networks to analyze pathological kidney images. We constructed a rat chronic kidney disease (CKD) model and used different drug interventions to study the pathological changes in the kidneys, which is convenient for machine in-depth learning and the construction of a recognition system. The reliability and credibility of the system were assessed by a blind comparative analysis. Microscopic image recognition and classification: Five pathological groups were subjected to three types of staining to obtain 15 image groups. Fifty jpg images were captured from each image group, so that 750 images were captured for training. The average hard disk space per image was 354 kb. Because the input image was 1000 pixels wide with a large resolution, multiple sampling was required to extract feature information. This implies that the level of span multiplication greatly affected the performance of the network during sampling. First, the ResPool samples with the same number of channels, followed by the output of a convolution layer, were assembled as the incremental channel. Thus, the feature extraction network of this work successfully implemented the idea of residual learning and did not introduce errors in the deep network to achieve the expected effect. The neural network model of this study designed a ResPool sampling structure based on the idea of residual learning, completed glomerular instance segmentation and damage analysis, and improved the accuracy of image recognition tasks.

Progressive multifocal leukoencephalopathy (PML) is a demyelination disease of the central nervous system (CNS) caused by viral infection with John Cunningham polyomavirus (JC virus, JCV). PML affects mainly patients with immunodeficiency. Since the diagnosis is often challenging, it requires the close cooperation of clinicians. Due to the lack of specific treatment of JCV infection leading to PML, the current treatment is based on reversing the immunosuppression. Here we present a case of a 58-year-old woman who was ultimately diagnosed with PML based on neuropathological analysis of stereotactic biopsy specimens.

Anterior nucleus of the thalamus deep brain stimulation (ANT DBS) offers a treatment option for patients with drug-resistant epilepsy (DRE). This treatment modality is particularly useful in cases of multifocal DRE originating from the frontal and temporal lobes. Here we present a 36-year-old epileptic patient who underwent ANT DBS implantation. The incidence of seizures dropped significantly after surgery, though the patient still experienced occasional seizure episodes. After 9 months, the patient sustained a head injury due to bilateral tonic-clonic seizures (BTCS), leading to the development of a chronic subdural hematoma (cSDH) and subsequent displacement of the ANT DBS electrodes. Following the evacuation of the left cSDH, MRI revealed properly positioned DBS electrodes, with no need for additional adjustments. The follow-up period was uncomplicated, showing a 68% reduction in focal impaired awareness seizures (FIAS) and an 80% reduction in BTCS at 24 months. To our knowledge, this is the first report of a patient who developed a cSDH with subsequent displacement of both DBS leads implanted in the ANT.

Introduction: Aim of the study was to explore the association between ferroptosis genes in peripheral blood and immune infiltration in epileptic patients.

Material and methods: Our study investigated epilepsy-related differentially expressed genes (DEGs) and differential ferroptosis genes in the peripheral blood of epilepsy patients. Additionally, we collected serum from 45 epileptic patients and 45 healthy individuals to detect ferroptosis-related indicators and validate the expression levels of randomly selected differential ferroptosis genes. Subsequently, we screened model-related genes by least absolute shrinkage and selection operator regression and constructed a diagnostic model. Moreover, we analyzed peripheral immune infiltration through single-sample gene set enrichment analysis, and assessed the correlation between model-related genes and FerroScore with immune infiltration in epilepsy.

Results: Epilepsy-related DEGs were markedly enriched in the immune pathway and may be involved in ferroptosis. According to our findings, glutathione was dramatically lower in epileptic patients, whereas the expression of ATG5 was significantly elevated. Furthermore, based on 26 model-related differential ferroptosis genes, FerroScore was constructed and exhibited favorable diagnostic performance (AUC: 0.573-0.763). Herein, seven genes (FBXW7, MYB, QSOX1, PARP15, RB1, PTGS2, and TFRC) showed a significant correlation with FerroScore. Finally, notable variations in peripheral immune infiltration were observed in epileptic patients, with PRR5 and FerroScore showing close associations with them.

Conclusions: Taken together, our observations suggest that in the peripheral blood of epileptic patients, FerroScore may help identify the occurrence of ferroptosis, while ferroptosis is strongly associated with immune infiltration. The study may shed novel light on the pathogenesis and treatment of epilepsy.

Introduction: This investigation evaluates the effectiveness and safety of stereoelectroencephalography (SEEG)-guided radiofrequency thermocoagulation (RF-TC) as a treatment modality for drug-resistant epilepsy.

Material and methods: A retrospective review of clinical data from 40 paediatric patients with drug-resistant epilepsy, who underwent SEEG-guided RF-TC at our Epilepsy Center between 2020 and 2022, was conducted. This review included the patients' medical history, imaging and electroencephalography results, surgical procedures, and follow-up outcomes.

Results: The duration of SEEG monitoring, accompanied by concurrent electrical stimulation tests, varied from 3 days to 4 weeks. Following RF-TC surgery, 4 patients demonstrated temporary neurological impairments, including central facial and tongue weakness, reduced limb strength, and challenges in fine motor hand movements. All these symptoms were related to lesions in the central region, but showed improvement within 2 weeks to 3 months post-surgery. There were no reported instances of status epilepticus, intracranial haemorrhage, or infections. During a follow-up period of 6 months to 2.5 years, seizure control was achieved in 25 patients (62.5%) at 6 months post-surgery, and a > 50% decrease in seizure frequency was observed in 10 patients. In 5 patients where seizure control was not achieved, the management of epilepsy seemed to be independent of factors such as age at surgery, duration of preoperative disease, seizure type, or negative MRI findings ( p > 0.05). Patients with controlled epilepsy exhibited cognitive improvement, with some demonstrating no EEG abnormalities upon follow-up and a decrease in antiepileptic medication.

Conclusions: SEEG-guided RF-TC appears to be a potentially effective and safe therapeutic approach for paediatric patients with drug-resistant epilepsy.

Introduction: The morbidity and mortality of spinal cord injury (SCI) are increasing year by year. It is of vital importance to ascertain the mechanism of SCI. Phosphoglycerate mutase family member 5 (PGAM5) is viewed as a molecular marker of SCI, but its specific role in SCI is elusive.

Material and methods: Following establishment of the SCI mouse model, the pathological examination of the spinal cord was initially assessed using H&E staining. PGAM5 expression in spinal cord tissues was appraised utilizing immunohistochemistry and RT-qPCR. Subsequently, after the expression of PGAM5 in SCI mice was inhibited by adenovirus transfection, the degree of SCI was determined, and the motor ability of hind limbs was estimated with the BBB score. In addition, the apoptosis of neurons, microglia activation and the generation of inflammatory cytokines in the spinal cord of mice were detected. Next, at the cellular level, PGAM5 expression was inhibited in the BV2 microglial cells induced by lipopolysaccharide (LPS), so as to explore the effects of down-regulation of PGAM5 on the activation, inflammation and apoptosis of neurons. Finally, western blot was applied for the appraisement of apoptosis signal-regulating kinase-1 (ASK-1)/p38/nuclear factor-kappa B (NF-kB) signaling-associated proteins.

Results: PGAM5 expression in SCI mice was found to be raised. PGAM5 expression in SCI mice was found to be raised. Inhibition of PGAM5 expression in SCI mice can significantly reduce spinal cord pathological injury, SCI-induced neuronal apoptosis, microglial cell activation and inflammation. The above regulatory process might be realized through the ASK-1/p38/NF-kB signaling pathway mediated by PGAM5.

Conclusions: Down-regulation of PGAM5 attenuated SCI-induced neuronal injury by inhibiting ASK-1/p38/NF-kB signaling.

Glioblastoma is a multifaceted and therapeutically challenging disease. Despite decades of ground-breaking research work, therapeutic options for the cure of glioblastoma are limited. A substantial amount of knowledge has been added to the complicated web of intertwined protein networks related to glioblastoma. Researchers have dissected a wide variety of signaling cascades, which play fundamental role in disease onset, progression and drug resistance. Recent technological advancements have changed our understanding of the signal specificity and revealed that discrete spatio-temporal activation profiles of the same effectors resulted in diverse physiological responses. Detailed mechanistic insights revealed that deregulated oncogenic pathways played an instrumental role in onset and progression of glioblastoma. Genomic and proteomic studies have unraveled the molecular underpinnings of the TGF/SMAD pathway in glioblastoma. Overall, we hope that this review will enable researchers and clinicians to develop a better understanding of the underlying mechanisms of glioblastoma. Comprehensive interpretation of multi-omics data in glioblastoma will not only enrich our understanding of the heterogeneous nature of glioblastoma but also galvanize the development of personalized clinical approaches.

In this study, we investigated whether changes in the expression of the a-synuclein gene occur and participate in post-ischemic brain neurodegeneration of Alzheimer's disease phenotype. The current study assessed the expression of the a-synuclein gene by RT-PCR after 10-minute brain ischemia in rats in CA3 area with survival at 2, 7, and 30 days and 6, 12, 18, and 24 months. Reduced gene expression was observed at 2 days, 6, and 24 months after ischemia. In the remaining observation periods, i.e., 7 and 30 days and 12 and 18 months, its expression was significantly above control values. In post-ischemic brain, where survival times ranged from 2 days to 2 years, we noted biphasic changes in overexpression of the a-synuclein gene in the CA3 area of the hippocampus. The presented data correlate very well with previous studies, which found an increase in protein levels in the brain and strong immunostaining for a-synuclein after ischemia. Finally, the results clearly indicate that changes in the expression of the a-synuclein gene play an important role in acute and secondary brain injury and the development of brain neurodegeneration after ischemia of Alzheimer's disease phenotype. Overall, studies show that a-synuclein is an attractive target for the development of new therapies to minimize ischemic brain damage and neurological dysfunction.