Folia neuropathologica最新文献

Introduction: Alzheimer's disease (AD) is classified as a neurodegenerative disorder without efficacious therapeutic interventions. Accumulating evidence has demonstrated the deposition of b-amyloid peptide (Ab) in the spinal cord in several mouse AD models. Neuregulin 2 (Nrg2), structurally homologous to neuregulin 1 (Nrg1), exerts a regulatory influence over various biological processes within the nervous system. However, the neuroprotective role of Nrg2 in the spinal cord in AD remains unclear.

Material and methods: Reverse transcription PCR (RT-PCR) was employed to confirm the expression of mutated amyloid precursor protein (APP) in APPswe mice. Immunohistochemical staining was used to compare the differences between wild-type and APPswe mice in APP and GFAP expression. We applied western blot to test the changes of ErbB4, Akt1, and Erk1/2 activation, as well as that of GFAP in response to recombinant Nrg2 (rNrg2) treatment in the spinal cord in APPswe mice.

Results: In the current study, we observed that mutated APP mRNA level was upregulated, and astrocytes were activated in the spinal cord of APPswe transgenic mice. rNrg2 treatment down-regulated astrocyte activation, as indicated by the reduced level of GFAP. Meanwhile, Nrg2 treatment enhanced the phosphorylation-mediated activation of ErbB4, Akt1, and Erk1/2 in most of the spinal cord segments.

Conclusions: These combined results suggest the involvement of astrocytosis in the spinal cord of APPswe transgenic mice. Neuregulin 2, when administered exogenously, may represent a potential strategy for preventing and treating AD-induced astrocytosis in the spinal cord.

Introduction: Intervertebral discs are generally known as the body's largest avascular structures. In the human body, there is not yet a collective resource characterizing intervertebral vascularization. When an intervertebral disc herniation occurs, new blood vessels proliferate in the capsule of the herniated tissue. In this study, we aimed to investigate intervertebral disc degeneration, neovascularization, and histopathological findings in patients who underwent surgical treatment.

Material and methods: The study was carried out by retrospective, double-blind examination of lumbar intervertebral disc tissue removed during the operation of 72 patients. To observe the structure of the disc, 5-6-micron-thick sections were taken, stained with hematoxylin and eosin (HE), and neovascularization and angiogenesis in the degenerated intervertebral disc tissue were examined microscopically.

Results: The results showed that neovascularization and bleeding measurements were not independent from each other, and there was a statistically significant association between them. Also, a higher level of neovascularization was found to be associated with higher bleeding and higher mononuclear inflammation.

Conclusions: With the development of degeneration in the intervertebral disc tissue, angiogenesis, neovascularization and mononuclear cell migration occur. It is predicted that proinflammatory cytokines cooperate with angiogenesis and mononuclear cells in the development of degeneration. There is currently no treatment to prevent intervertebral disc degeneration. In order to develop successful treatments to prevent this disease, its pathogenesis needs to be understood.

This study assessed the effect of batatasin-III on cerebral microvascular endothelial cell (EC) injury. Endothelial cell injury was induced in isolated cells by oxygenglucose deprivation/reperfusion (OGD/R) conditions. During 4 h of OGD insult, cells were treated with batatasin-III at different concentrations, and an MTT assay was performed to estimate cellular viability. Nitric oxide, mitochondrial membrane potential (MMP), and release of lactate dehydrogenase (LDH) were determined in ECs exposed to OGD/R. Cerebral ischemia was performed to induce brain injury to assesses the effect of batatasin-III. There was improvement in the viability of cell and reduction of release of LDH in batatasin-III-treated, OGD/R-induced EC injury. Treatment with batatasin-III ameliorates the altered integrity of mitochondrial membrane and expression of apoptotic proteins in OGD/R injured ECs. Apoptosis of neuronal cells and infarct size were reduced in batatasin-III-treated middle cerebral artery occlusion (MCAO) rats, and pathological changes were reversed. Based on study data, we concluded that cerebral injury was attenuated by batatasin-III treatment by reducing oxidative stress and cellular apoptosis.

Nicotinamide adenine dinucleotide (NAD + ) supplementation attenuates demyelination in the experimental autoimmune encephalomyelitis (EAE) model. The aim of the study was to confirm the therapeutic effect of NAD + on the EAE model and investigate its protective mechanism. Mice were divided into 3 groups: EAE, EAE + NAD + , and Control (Ctrl). EAE and EAE + NAD + groups were induced with myelin oligodendrocyte glycoprotein (MOG) to initiate the demyelination process. The EAE + NAD + group received an NAD + injection at a dosage of 250 mg/kg/day. Clinical, neuroinflammation, and neurodemyelination scores were monitored. At the peak of onset, animals were euthanized, and mRNA expression level in the spinal cord was tested. NAD + supplementation promoted the conversion of regulatory T cells (Tregs) into T helper 17 (Th17) cells with increased concentrations of NAD + . NAD + alleviated neuroinflammation, attenuated central nervous system (CNS) demyelination, and improved the disease score of EAE mice. NAD + promoted expression of the cytokine interleukin 17A (IL-17A).

Introduction: Gliomas are among the most aggressive brain tumors, with limited treatment options and poor patient outcomes. Recent studies suggest that miRNAs play a crucial role in tumor development and progression. This study aimed to leverage transcriptomics data to identify critical miRNAs involved in glioma, which may serve as potential therapeutic targets.

Material and methods: GO and KEGG analyses were used to investigate target genes. Protein-protein interaction analysis identified CCND1 as a key gene, and miR-129-5p was selected for its interaction with CCND1. The expression levels of miR-129-5p and CCND1 in glioma samples and cells were measured. Dual-luciferase assays confirmed their targeting relationship. Functional assays (CCK-8, wound healing, Transwell) were conducted in U87 cells, and the impact on the PI3K/AKT pathway was analyzed by western blot. In vivo studies were performed in nude mice.

Results: miR-129-5p expression was significantly reduced in glioma tissues and U87 cells compared to normal tissues or cells, while CCND1 was markedly increased. Dual-luciferase reporter assays confirmed that miR-129-5p directly targets CCND1. Overexpression of miR-129-5p reduced U87 cell proliferation, migration, and invasion, and inhibited the PI3K/AKT pathway. In vivo, miR-129-5p suppressed tumor growth and improved mouse survival.

Conclusions: miR-129-5p may exert a tumor-suppressive effect in glioma by targeting CCND1 and suppressing the PI3K/AKT signaling pathway.

Introduction: Stathmin, recognised as the protein associated with the disassembly of microtubules, plays a vital role in the modulation of human fear as well as anxiety responses. However, it is unclear whether stathmin regulates the specific mechanism of disruption of fear-associated memory resulting from posttraumatic stress disorder (PTSD). This study aims to observe the impact of stathmin on deficit in fear-based memory during PTSD and investigate the underlying mechanisms involved, in order to establish an empirical foundation for elucidating the molecular mechanisms underlying the pathogenesis of PTSD.

Material and methods: We used an single prolonged stress (SPS) protocol to induce the PTSD in the rat model. Open field test and forced swimming test were used to examine the anxious and fearful behaviours exhibited by the rats. STAT3/stathmin signalling-related expressions were assessed through immunofluorescence, immunohistochemical, RT-qPCR and Western blotting. Stathmin and STAT3 binding activity was detected by molecular docking. Amygdala apoptosis was detected by TUNEL staining.

Results: In this study, while stathmin gene expression in amygdala was significantly downregulated, after 7 days of SPS, activation of STAT3 was observed in the rats' amygdala, accompanied by a notable increase in the apoptosis rate. Consequently, the rats exhibited heightened fear and anxiety responses. However, the above results were reversed after overexpression of the stathmin gene. In addition, following the administration of the STAT3 inhibitor, WP1066, there was a notable reduction in the apoptosis rate, leading to decreased levels of fear and anxiety in rats exposed to SPS. In rats exposed to SPS, administered WP1066, and injected with adenovirus expressing stathmin-targeted siRNA into the amygdala to make the inhibition of stathmin expression partially counteracted the protective effect of WP1066.

Conclusions: The findings above suggest that SPS could potentially modulate the stathmin gene's expression by activating the STAT3 pathway, subsequently leading to apoptosis in amygdala cells. This sequence of events ultimately contributes to the PTSD rat model fear memory impairment.

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.

Sepsis-associated brain injury can lead to severe neurobehavioral and cognitive impairments due to inflammation, oxidative stress, and blood-brain barrier (BBB) dysfunction. Remimazolam (RM), a novel benzodiazepine, may have therapeutic potential for managing these complications. This study aimed to explore the therapeutic effects and potential molecular mechanisms of RM on BBB injury and brain injury in septic rats. Septic rat models were constructed using cecal ligation and puncture (CLP), with 75 rats randomly assigned to five groups (15 rats per group). RM (5 mg/kg, 10 mg/kg, and 20 mg/kg) was injected intraperitoneally to treat the rats. Neurobehavioral and cognitive functions were evaluated via neurological scores, water maze, and Y-maze tests. Brain water content was measured using the dry-wet weight method, and BBB permeability was assessed with Evans blue staining. Oxidative stress and inflammatory markers were detected using enzyme-linked immunosorbent assays and biochemical kits. Western blot analysis was performed to evaluate RM's effects on TLR4/NF-κB pathway proteins. RM treatment alleviated neurobehavioral and cognitive dysfunction while reducing inflammation and oxidative stress in septic rat brain tissue, with 10 mg/kg RM showing the greatest efficacy. RM also reduced brain water content and BBB damage, downregulating TLR4/NF-κB pathway proteins. These findings suggest that RM can effectively alleviate blood-brain barrier and brain injury in septic rats by inhibiting the TLR4/NF-κB pathway. The therapeutic effects observed may pave the way for future clinical research into RM's use for managing sepsis-associated brain injury.