Folia neuropathologica最新文献

Neuropathic pain (NP), a severe nervous system ailment, is affected by microRNA's role in microglial polarization. MiR-182 helps ease this pain, particularly from spared nerve injury, but its regulatory mechanism remains poorly understood. In this study, we first observed that lipopolysaccharide (LPS) triggered M1 polarization, leading to an increase in CD86, iNOS, p-PI3K and p-AKT and a decrease in CD206, Arg-1 and miR-182 expression levels. Following that, BV-2 cells underwent transfection with miR-182 mimics or inhibitors to examine the influence of miR-182 on the polarization states and PI3K/AKT signaling. The inflammatory cytokines were determined using ELISA assay. Overexpression of miR-182 decreased pro-inflammatory cytokines, upregulated the expression of CD206 and Arg-1, while downregulating CD86, p-PI3K and p-AKT in LPS-induced BV-2 cells, which were abolished by the PI3K/AKT activator 740Y-P. The in vivo data demonstrated that the pain level in an NP rat model, triggered by chronic constriction injury (CCI) surgery, was markedly decreased by the intrathecal administration of lentiviral (LV)-mediated miR-182, as measured by paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL). Additionally, miR-182 reduced the levels of pro-inflammatory cytokines (TNF-a, IL-1b, and IL-6) and the number of M1-polarized microglia in the NP rat. However, the neuroprotective benefits of miR-182 were negated when 740Y-P was administered. In conclusion, these data suggest that miR-182 can alleviate NP and neuroinflammation by promoting the shift from M1 to M2 phenotype polarization via suppressing the PI3K/AKT signaling pathway.

Introduction: Glioma is the most prevalent primary brain tumor, causing significant mortality and morbidity. lncRNAs have great potential in tumor-targeted therapy, including for glioma via sponging microRNAs. Previous studies have shown that LINC00900 and miR-186-5p likely play a significant role in glioma progression. However, the relationship between them has not been elucidated. The purpose of this study was to explore the role of LINC00900 in the prognosis of gliomas and its underlying molecular mechanisms.

Material and methods: Matched tissue specimens were collected from 107 patients with gliomas. The level of LINC00900 was monitored by qRT-PCR, and a series of statistical analyses were performed to predict the correlation between LINC00900 and clinicopathologic features. Additionally, the dual-luciferase reporter assay was used to assess the interplay between LINC00900 and miR-186-5p. The regulatory effect of miR-186-5p on LINC00900 tumor promoter role was also estimated. Cell metastasis and proliferation of glioma cells were evaluated by Transwell assay and CCK8, respectively.

Results: Upregulation of LINC00900 was noted in glioma tissues. A significant association was found for LINC00900 with WHO grade, tumor size, and Karnofsky performance status (KPS) of glioma patients. LINC00900 was found to be associated with poor patient prognosis. Additionally, LINC00900 negatively regulated the level of miR-186-5p and facilitated the proliferation and metastasis of glioma cells. The inhibitory effect caused by decreased LINC00900 in glioma could be reversed by a reduced level of miR-186-5p.

Conclusions: LINC00900 in glioma was identified as an indicator of poor prognosis. In the mechanism, LINC00900 promoted glioma cell proliferation and metastasis by regulating miR-186-5p negatively.

Introduction: Spinal cord stimulation (SCS) is considered an efficient and safe method of treating intractable chronic pain from various origins such as persistent spinal pain syndrome (PSPS) or complex regional pain syndrome (CRPS). The complications related to SCS therapy are usually classified as mechanical or biological. Myelopathy related to dense scar tissue formation around epidural paddle electrodes implanted for SCS therapy is extremely rarely reported. We have studied all reported cases of surgical management of this complication and we sought to find predisposing factors responsible for development of this rare but dangerous complication.

Case summary: We report on 2 cases of thoracic spinal cord compression by scar tissue encountered around epidural electrodes implanted for SCS. Both patients had their implantable pulse generators (IPGs) removed due to biological complications (skin erosions with subsequent infection at IPG site confirmed in one patient). During the waiting time for further placement of new IPGs, both patients developed myelopathic symptoms. Magnetic resonance imaging (MRI) in both cases showed severe compression of the spinal cord by scar tissue around the electrode. Surgical decompression resulted in full and partial recovery in each patient. In both cases, during surgery, excessive epidural fibrosis was encountered, without signs of active infection. Surgical decompression in patient 1 resulted in full recovery, while patient 2 had a complicated postoperative course with partial recovery.

Conclusions: To our knowledge, both cases constitute extremely rare complications of SCS therapy resulting in thoracic spinal myelopathy. The predisposing factors found in our patients were surgically placed paddle electrodes with a prior history of IPG removal due to biological complications (skin erosions and infection). In the literature, surgical electrodes placed in the cervical spine rather than the thoracic spine were more often found to result in excessive epidural scarring, resulting in spinal compression syndromes. Prompt surgical decompression with scar tissue removal is mandatory to achieve full recovery.

Brainstem gliomas in adults are a rare and heterogeneous group of brain tumours, which account for less than 2% of all adult gliomas and usually involve the pons (60-63%). The medulla oblongata and the midbrain are the least common locations of brainstem gliomas (25% and 12-15%, respectively). Survival and overall prognosis depend on the underlying pathology and pathological tumour grade. The authors present a female patient with medulla oblongata rapidly growing brainstem glioma (documented in a series of brain MRI examinations), which resulted in quick progression of neurological symptoms with cardiopulmonary insufficiency and death. The rapid growth of this lethal lesion and clinical deterioration made it impossible to perform stereotactic biopsy and implement optimal oncological treatment. Neuropathological brain and spinal cord postmortem examination revealed glioblastoma IDH-wildtype CNS WHO G4.

Introduction: Glioma, as the deadliest malignant tumor, is one of the most difficult problems in medicine. This study aims to further elucidate the molecular mechanism of glioma development and explore possible miRNAs as targets for glioma prognosis and molecular therapy.

Material and methods: RT-qPCR was used to determine the expression of miR-3188 in glioma tissues and cells. The relationship between miR-3188 and pathological features, as well as its prognostic importance, were examined using the chisquare test and Cox regression analysis. The dual luciferase reporting assay was utilized to confirm the targeting of miR-3188 and MAPK1. Transwell assay and Cell Counting Kit-8 (CCK-8) assays were used to identify the roles that miR-3188 plays in cell metastasis and proliferation, respectively.

Results: Research has revealed downregulation of miR-3188 in the tissues and cells of glioma, which is strongly correlated with the tumor size, Karnofsky Performance Status (KPS) score, World Health Organization (WHO) grade, and patients' survival rate in glioma. Four downstream target genes were screened by bioinformatics analysis, among which MAPK1 was abnormally expressed in glioma, and was negatively correlated with miR-3188. When miR-3188 was overexpressed, the malignant behavioral activity of glioma cells was significantly decreased; however, the inhibitory effect was reversed when MAPK1 was overexpressed.

Conclusions: miR-3188 is a potential predictor of malignant development and poor prognosis in glioma patients and targets MAPK1 to inhibit the progression of glioma.

Burkitt lymphoma (BL) is a specific, rare (1-2% of all cases of lymphoma) and aggressive type of B-cell non-Hodgkin lymphoma. If BL recurs during treatment, it usually becomes drug-resistant to subsequent treatment regimens and the prognosis is very poor. We present an extremely rare case of recurrent BL infiltrating the central nervous system (CNS) in a 27-year-old HIV-infected patient who had completed GMALL-B-ALL/NHL2002 protocol treatment 4 months earlier. Radiological and neuropathological examinations of cerebral recurrence of BL, followed by specialized oncological treatment, were discussed. Currently, with antiretroviral therapy and intensive immunochemotherapy for the immunodeficiency-associated BL variant, disease recurrence in the CNS is extremely rare. The magnetic resonance imaging (MRI) findings and laboratory tests are unspecific, as shown in the present case. The final diagnosis can be established properly by performing image-guided stereotactic biopsy or flow cytometry with cytology examination of cerebrospinal fluid. After confirmation of isolated cerebral recurrence of BL, the patient received intensive treatment according to the R-MIV protocol and achieved a second complete remission.

Introduction: Glioma is a highly aggressive malignant tumor with high mortality, which is prone to metastasis and recurrence. This study investigated the biological function and related mechanism of action of the long non-coding RNA SNHG22 (lncRNA SNHG22; SNHG22) on glioma cells and its prognostic value.

Material and methods: The relative expression levels of SNHG22 and miR-27b-3p in the included glioma patients were detected by real-time quantitative PCR (RT-qPCR). The cell counting kit-8 (CCK-8) proliferation assay and Transwell assay confirmed the effect of knockdown of SNHG22 on the biological function of glioma cells. Luciferase activity characterized the mechanism of SNHG22 targeting miR-27b-3p. Additionally, Kaplan-Meier and multivariate Cox analyses were performed to evaluate the effect of SNHG22 on patient survival.

Results: In glioma tissues and cells, compared to normal samples as controls, SNHG22 expression was increased and the expression of miR-27b-3p was decreased. Silencing SNHG22 suppressed the proliferation, migration and invasion levels of glioma cells. SNHG22 directly targets miR-27b-3p to regulate tumor progression. Low expression of SNHG22 was more conducive to the survival of patients than high expression of SNHG22.

Conclusions: The lncRNA SNHG22 regulated the progression of glioma by targeting miR-27b-3p, which reflected the prognostic potential of SNHG22 and provided a meaningful theoretical reference for the treatment of glioma patients.

Herein, we report the first case of mild malformation of cortical development with oligodendroglial hyperplasia and epilepsy (MOGHE) in Bulgaria. It is a newly recognised clinico-pathological entity with medically intractable focal epilepsy in paediatric patients. The patient of interest is a 9-year-old boy who has been suffering from refractory epilepsy since the age of three. Positron emission tomography revealed a consistent hypometabolism with maximum in the orbitofrontal and fronto-opercular cortex, as well as in the adjacent anterior insula and the anterior temporal regions. A left frontal corticotomy anterior from the precentral sulcus, left insulectomy and temporal disconnection were performed. Pathomorphological examination of the material from the resected brain tissues demonstrated oligodendroglial hyperplasia with blurring of grey-white-matter boundaries and presence of subcortical heterotopic neurones. Eighteen months post-surgically the patient is seizure-free and drug-free. The observed oligodendroglial hyperplasia with increased proliferative activity and heterotopic neurones in the white matter with blurring of grey-white-matter junctions are the histopathological hallmarks of MOGHE. More new cases are needed to establish further data about this distinct entity in frontal lobe epilepsy.

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.

Paclitaxel (PTX) is a potent chemotherapy drug commonly used to treat various solid tumours, including breast and ovarian cancers. However, its effectiveness in treating IDH-wildtype glioblastoma has been limited due to challenges crossing the blood-brain barrier (BBB). Glioblastoma remains one of the most difficult cancers to treat, with a median survival of 15 months from diagnosis. Recent advancements in nanotechnology have led to innovative PTX delivery systems that enhance its bioavailability and enable targeted brain therapy. These include nanoparticles composed of biocompatible materials that enhance drug solubility and targeting while addressing BBB permeability. Examples include albumin-bound PTX (Abraxane), self-assembled nanoparticles from natural bioactive molecules, poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles, and hydrophilic nano-prodrugs, each showing promise in enhancing the therapeutic impact of PTX. These systems utilize biocompatible nanoparticles that enhance drug solubility, targeting, and BBB permeability. Numerous ongoing clinical trials and preclinical studies are exploring the efficacy of these nanocarrier systems in overcoming drug resistance and improving patient outcomes. The latest advancements in PTX-based nanotherapeutics for glioblastoma focus on overcoming the BBB, developing nanoparticle delivery systems, and evaluating the clinical significance of these developments.