Folia neuropathologica最新文献

Autoimmune/immune-mediated central nervous system (CNS) diseases are chronic, inflammatory, autoimmune diseases, such as multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and autoimmune encephalitis (AE). A common pathological feature of these diseases is the targeting of the host's immune system against autoantigens expressed by the CNS. In recent years, immunomodulatory therapeutic drugs and methods with different targets have emerged. Therefore, obtaining a more comprehensive and in-depth understanding of the characteristics, adverse reactions and indications of existing therapeutic drugs is essential to develop individualized therapies based on each patient's characteristics, delay the progression of disorders and enhance the life quality of these patients. Although MS, NMOSD, and AE are all associated with immune inflammation, there are considerable differences in clinical treatment. Certain drugs may be approved for only one of these diseases, while other drugs may be suitable for all three. This review systematically describes the characteristics and scope of application of various drugs, including potential drugs under development, as well as non-drug therapeutic approaches.

Introduction: This study aimed to investigate the effect of sequential treatment with butylphthalide on neurological and cognitive functions and collateral circulation in patients with acute cerebral infarction (ACI).

Material and methods: A total of 62 patients with ACI treated in our hospital between March 2021 and May 2021 were selected by convenience sampling and divided into the observation group ( n = 31) and the control group ( n = 31) using a random number table. Patients in the control group received conventional treatment, and those in the observation group received sequential treatment with butylphthalide in addition to conventional treatment. Neurological and cognitive functions and collateral circulation were compared between the two groups.

Results: Improvements in the neurological, activities of daily living (ADL) and cognitive functions were better in the sequential treatment group than in the control group, which received conventional treatment. Statistically significant differences in the National Institutes of Health Stroke Scale (NIHSS), Modified Barthel Index (MBI), Lawton Instrumental Activities of Daily Living (Lawton IADL), Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores were also noted between the two groups (F NIHSS treatment = 142.414, p < 0.001; F MBI treatment = 143.662; F IADL treatment = 137.624; F MMSE treatment = 87.418, p < 0.001; F MoCA treatment = 122.724, p < 0.001). Collateral circulation assessment showed that the blood flow velocities of the anterior cerebral artery (50.21 ±7.56 vs. 44.96 ±8.33, t = 2.598, p = 0.012), middle cerebral artery (34.52 ±6.29 vs. 21.74 ±4.81, t = 8.986, p < 0.001) and posterior cerebral artery (37.92 ±6.36 vs. 34.44 ±6.74, t = 2.091, p = 0.041) after treatment were statistically significantly higher in the observation group than in the control group.

Conclusions: Sequential treatment with butylphthalide improves the neurological and cognitive functions and collateral circulation, as well as the ADL of patients with ACI, with higher efficacy than conventional treatment and without compromising safety.

This study aimed to identify potential therapeutic targets for spinal cord ependymoma (SCE) and key signaling pathways associated with the transforming growth factor b (TGF-b) signaling pathway through bioinformatics analysis, molecular biology validation, and clinical characteristics. Differentially expressed genes (DEGs) in SCE were identified using the limma package in R, and a Venn diagram was created to obtain the intersection of TGF-b signaling pathway-related genes and DEGs. Next, the clusterProfiler package was employed for enrichment analysis of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. Also, a protein-protein interaction network of DEGs was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins website, and Cytoscape was used to visualize and screen the top 20 key genes. Additionally, quantitative real-time polymerase chain reaction and western blot were used to validate the mRNA and protein expression levels, respectively, of SMAD4, TGFB1, and TGFB receptor 1 (TGFBR1) in clinical samples. A total of 61 differentially expressed TGF-b signaling pathway-related genes were associated with 1) biological processes, such as the transmembrane receptor protein serine/threonine kinase signaling pathway, TGF-b receptor signaling pathway, and pathway-restricted SMAD protein phosphorylation; 2) cell components, such as the plasma membrane signaling receptor complex and collagen-containing extracellular matrix; and 3) molecular function, such as SMAD binding, growth factor binding, and cytokine binding. The protein-protein interaction network consisted of 57 nodes and 339 edges, and three key genes (SMAD4, TGFB1, and TGFBR1) were screened. The TGF-b and Hippo signaling pathways may have potential roles in SCE progression, and SMAD4, TGFB1, and TGFBR1 are potential key genes.

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.

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: 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.