Folia neuropathologica最新文献

Introduction: The aim was to explore the factors influencing hemorrhagic transformation (HT) after mechanical thrombectomy (MT) in acute anterior circulation large vessel occlusion stroke (ALVOS) and establish a corresponding prediction model.

Material and methods: A retrospective study was conducted on 180 ALVOS patients who underwent MT in our hospital between May 2022 and December 2023. The patients were divided into a bleeding group (134 cases) and a non-bleeding group (46 cases) based on whether there was intracranial hemorrhage in the immediate follow-up head CT after surgery. Logistic regression analysis was performed to explore the factors influencing HT after MT in ALVOS patients. A logistic regression prediction model based on risk factors was constructed. The predictive ability of the model was validated using receiver operating characteristic (ROC) curves.

Results: Significant differences were detected between the bleeding group and the non-bleeding group in terms of age, diabetes, NIHSS score on admission, time from onset to admission, time from onset to vascular recanalization, number of embolectomy attempts, and application of tirofiban (p < 0.05). Diabetes, NIHSS score on admission, time from onset to admission, time from onset to vascular recanalization, number of embolectomy attempts, and application of tirofiban were all significant factors influencing HT in ALVOS patients who underwent MT (p < 0.05). The logistic risk prediction model was constructed using the following model: Logit (P) = 0.625 × combined diabetes + 0.071 × NIHSS score + 0.035 × onset to hospital time + 2.321 × onset to vascular recanalization time + 1.461 × number of embolectomy attempts + 0.993 × application of tirofiban. The model had the likelihood ratio chi square (c2) = 196.85, DF = 6, p 2.03, the AUC was 0.882, 95% CI was 0.792-0.175, Z = 20.331, p < 0.001, with the predictive sensitivity of 85.35% and the specificity of 85.74%.

Conclusions: Age, diabetes, NIHSS score on admission, time from onset to admission, time from onset to vascular recanalization, number of thrombectomy attempts, and use of tirofiban were independent risk factors for HT after MT in ALVOS patients. A logistic risk prediction model incorporating independent risk factors had some predictive value for HT after thrombolysis.

Collision tumors, a rare phenomenon wherein two tumors with different histological features appear in the same anatomical region, present a challenging clinical diagnosis, particularly in the context of intraspinal collision tumors. This study reports the clinical data of a patient with an intraspinal collision tumor composed of schwannomas and ependymomas. A 47-year-old woman was admitted to the hospital with a six-month history of lumbosacral pain and numbness in both lower extremities. Lumbar magnetic resonance imaging (MRI) revealed two space-occupying lesions in the L1-2 spinal canal, which were initially diagnosed as two separate neurogenic tumors. Subsequent pathological examination revealed a collision tumor comprising a schwannoma and ependymoma. Intraspinal collision tumors, especially those combining schwannoma and ependymocytoma, are exceedingly rare. When two separate or conjoined tumors are present at the same anatomical site, the possibility of a collision tumor should be considered, despite its rarity. Interestingly, it was found that vertebral collision tumors tend to involve hemangiomas, whereas intraspinal collision tumors predominantly involve schwannomas.

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: Ischemic stroke (IS) is a disease caused by blood circulation disorders in the brain, ischemia, and hypoxia, resulting in ischemic necrosis or softening of localized brain tissue. Lipoic acid (ALA) is effective in resisting oxidative stress and alleviating the inflammatory response. This study evaluated the mechanism and effects of ALA on neurovascular unit remodeling after cerebral infarction.

Material and methods: In male C57BL/6 mice, cerebral infarction was induced using distal middle cerebral artery occlusion (dMCAO). In an in vitro model, cells were allocated to control, model, low dose, medium dose, and high dose groups. Infarct volume analysis, Evans blue extravasation, and enzyme-linked immunosorbent assay (ELISA) kits were used to evaluate the effects of ALA on IS. Cell Counting Kit-8 (CCK-8), 5-ethynyl 2'-deoxyuridine staining (EDU) staining, Western blot and immunohistochemistry were used to evaluate the mechanism of ALA in IS.

Results: This study found that the cerebral infarct volume of the ALA treatment group was similar to dMCAO mice. Treatment with ALA reduced the area of Evans blue compared with dMCAO mice at 7 days, and promoted astrocyte and pericyte proliferation in the peri-infarct area at 28 days. Meanwhile, treatment with ALA also increased vascular endothelial growth factor (VEGF), angiopoietin (Ang)-1 and claudin-5 protein expression levels, suppressed Ang-2 and matrix metalloproteinase-9 (MMP-9) protein expression levels, reduced neuronal apoptosis inhibitory protein (NAIP), leucine-rich repeat (LRR), and PYD domain-containing protein 3 (NLRP3) expression levels, and induced phosphorylated-adenosine monophosphate-activated protein kinase (p-AMPK) protein expression levels in cerebral infarction mice (all p < 0.05). On the other hand, ALA restored cell growth and the number of EDU cells, promoted cell migration, elevated superoxide dismutase (SOD) activity, reduced reactive oxygen species (ROS) and malondialdehyde (MDA) levels, and inhibited inflammation levels in the in vitro model (all p < 0.05). Treatment with ALA also suppressed NLRP3 and Ang-2 protein expression, reduced MMP-9 protein expression, and induced VEGF, Ang-1, claudin-5, and p-AMPK protein expression levels in the in vitro model (all p < 0.05).

Conclusions: ALA improved neurovascular unit remodeling after cerebral infarction through anti-inflammation effects via the AMPK/NLRP3 signaling pathway.

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.

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.

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.

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: Triggering receptor expressed on myeloid cells 2 (TREM2), part of the immunoglobulin superfamily, is implicated in various malignancies. However, its role in glioma formation remains unclear. Our study uncovered a potential mechanism involving TREM2.

Material and methods: The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) datasets were utilized to assess the expression levels of TREM2 and DNAX-activating protein of 12 kDa (DAP12), explore their relationship, and evaluate their impact on patient prognosis. Western blotting was used to measure TREM2 expression in different glioma grades. Co-immunoprecipitation (Co-IP) was used to examine TREM2 and DAP12 interaction. Cell proliferation, invasion, and apoptosis were assessed via the cell proliferation test, cell invasion assay, and flow cytometry. An intracranial xenograft model was created by injecting tumor cells into nude mice. Mice injected with si-DAP12-transfected or non-transfected glioma cells were treated with 740Y-P, followed by survival analysis and immunohistochemistry.

Results: TREM2 and DAP12 were overexpressed in gliomas, with high levels associated with lower overall survival (p < 0.05 and p < 0.01). There was a strong positive correlation between TREM2 and DAP12 expression (p < 0.0001). TREM2 positively regulated DAP12, forming a complex that influenced glioma cell proliferation, apoptosis, and invasion (p < 0.05, p < 0.01, and p < 0.001). DAP12 knockdown significantly inhibited proliferation and invasion while promoting apoptosis of glioma cells, linked to the PI3K/AKT signaling pathway (p < 0.05 and p < 0.01). 740Y-P treatment counteracted the effects of DAP12 knockdown (p < 0.05, p < 0.01, p < 0.001, and p < 0.0001). In vivo, DAP12 knockdown inhibited glioma tumorigenicity (p < 0.001).

Conclusions: TREM2 positively regulates DAP12 and forms a complex that impacts glioma development via the PI3K/AKT pathway. Targeting the TREM2/DAP12 complex presents a potential therapeutic approach for gliomas.

Introduction: A molecular sequencing and phenotyping study was conducted on chemokines CCL2, CCL5, and CXCL10 to assess the relation to multiple sclerosis (MS).

Material and methods: The molecular detection study included extractions of DNA from the blood of cases and a control group, as well as amplification and confirmation of all extracted DNA. The 490-bp primer-size PCR product corresponded to CCL2, the 481-bp primer-size PCR product corresponded to CCL5, and the 310-bp primer-size PCR product corresponded to CXCL10.

Results: DNA sequencing of CCL2, CCL5, and CXCL10 showed that there was convergence between the obtained results and data from the GenBank database (NCBI) with 99% identity (439/445) in the forward CCL2 sequence, which had a single transition mutation, GGT to GGG. In addition, the reverse CCL2 showed 99% identity (426/427) when compared with the GenBank database (NCBI), which found a single deletion mutation, TGA to GGG. There was convergence between the studied CCL5 isolated and that of the GenBank database (NCBI) with 99% identity (443/447) in the forward CCL5. Four mutations were recorded: three transversions - TTT to TTA, AAA to AAT, and GCC to GCA - and one deletion, TGA to TGG. On the other hand, the reverse CCL2 showed 99% identity (436/439) when compared with the GenBank database (NCBI), with three mutations: two deletions - TGA to TG-, and CCA to CC- - and one transversion, ATT to ATA. Also, there was convergence between the studied CXCL10 isolated and that of the GenBank database (NCBI), with 98% identity 64/65 in the forward CXCL10 and one transversion mutation, GGT to GGG.

Conclusions: New genes for the chemokines CCL2, CCL5 and CXCL10 have been recorded. The results were registered in the NCBI database under accession numbers LC727557, LC727558, and LC727558, respectively. The study revealed the important roles of chemokines in the pathogenesis of MS, suggesting their potential as targets for future therapy.