Folia neuropathologica最新文献

Introduction: Postherpetic neuralgia (PHN) is one of the common refractory neuropathic pains. Oral drug treatment has great side effects and poor efficacy. To study the efficacy of computed tomography (CT)-guided pulsed radiofrequency (PRF) targeting dorsal root ganglion (DRG) and platelet-rich plasma (PRP), this retrospective observation was performed.

Material and methods: All patients with PHN were divided into the control group, PRF group, and PRF + PRP group based on their different treatment methods. The control group (45 cases) received drug treatment, the PRF group (45 cases) received CT-guided PRF treatment targeted to DRG, and the PRF + PRP group received PRF and PRP treatment. The changes of the numeric rating scale (NRS), Pittsburgh sleep quality index (PSQI) levels, and short form 36 health survey questionnaire (SF-36) before treatment and 7 days, 14 days, 30 days, and 90 days after treatment were compared among three groups.

Results: NRS and PSQI scores in the PRF + PRP group were lower than those in the PRF group and control group at 90 days after treatment ( p < 0.001). At 90 days after the operation, the scores of SF-36 in the PRF + PRP group were obviously elevated compared with the data of the control group and PRF group ( p < 0.001).

Conclusions: The pain degree, quality of sleep of patients, and quality of life with PHN were significantly improved after PRF combined with PRP treatments.

Introduction: To systematically analyse the relationship between sleep apnoea and the risk of dementia and assess the methodological quality of the most recent research evidence.

Material and methods: The PubMed, Embase and Cochrane Central Register of Controlled Trials databases were searched for relevant studies. We analysed hazard ratio (HR) or risk ratio values corresponding to random-effects models and their 95% confidence intervals (CI).

Results: We included 15 studies, which involved a total of 5,207,312 participants. Compared with individuals without sleep apnoea, those with sleep apnoea had a significantly increased risk of developing all-cause dementia, with an HR of 1.34 (95% CI: 1.17-1.53, p < 0.001, I 2 = 30%). Similarly, sleep apnoea significantly increased the risk of developing Alzheimer's disease and Parkinson's disease, with HRs of 1.28 (95% CI: 1.16-1.41, p < 0.001, I 2 = 22%) and 1.64 (95% CI: 1.47-1.82, p < 0.001, I 2 = 25%), respectively. However, the presence of sleep apnoea did not affect the incidence of vascular dementia, with an HR of 1.36 (95% CI: 0.88-2.10, p = 0.16, I 2 = 50%). Funnel plots showed an approximately symmetrical distribution for both types of data, suggesting no significant publication bias. In addition, sensitivity analyses on the overall results showed that there was still some heterogeneity among studies.

Conclusions: The common condition of sleep apnoea is significantly associated with the risk of developing dementia, particularly all-cause dementia, Alzheimer's disease and Parkinson's disease, but it does not significantly impact the risk of vascular dementia.

Introduction: There has been an increasing trend in spinal surgery interventions in recent years. Low back pain is a disorder that is seen at least once in the lifetime of approximately 80% of the general population. Today, neurosurgeons perform operations including laminectomy for various reasons. Epidural fibrosis is a scar tissue that develops after posterior spinal surgery. Various synthetic and organic materials have been used in experimental studies to prevent epidural fibrosis in laminectomy defects. In this study we aimed to investigate and observe histopathologically the effectiveness of cyclooxygenase inhibitor drugs; tenoxicam and diclofenac sodium in the experimental rat laminectomy model in preventing the postoperative spinal epidural fibrosis.

Material and methods: In this study, 32 Wistar-Albino female rats were used. 8 mg/kg tenoxicam and 1.5 mg/kg diclofenac sodium were applied on the dura with an absorbable gelatin sponge. After decapitation, L1-L4 laminectomy area was totally removed and histopathological examination was performed.

Results and conclusions: It has been shown that the topical application of diclofenac sodium and tenoxicam, which are selective Cox inhibitor drugs, prevents fibroblast migration by forming a local barrier and Cox inhibitors are caused by the inhibition of prostanoids, which are inflammatory mediators.

A large body of evidence has shown that the amyloid b peptide oligomers (Abo) are predominantly responsible for the neurodegeneration/cognitive impairments in Alzheimer's disease (AD). Abo cause mitochondrial dysfunctions leading to an imbalance between pro- and antiapoptotic proteins and finally to neuronal apoptosis. Further, Abo trigger overactivation of microglia followed by enhanced release of proinflammatory cytokines, which exacerbates neurotoxicity of Abo. The above-mentioned alterations are accompanied by disturbed metabolism of prosurvival bioactive sphingolipid, sphingosine-1-phosphate (S1P), and S1P-dependent signalling via specific receptors (S1PR1-5). In the present study, we investigated for the first time the influence of selective - ponesimod (S1PR1), CYM5541 (S1PR3), CYM50308 (S1PR4), A971432 (S1PR4), siponimod (S1PR1,5) - and nonselective - phosphorylated fingolimod/pFTY720 (S1PR1,3-5) - S1P receptor modulators on cell viability, mitochondrial membrane potential (MMP) and expression of genes encoding S1P receptors, pro- and antiapoptotic proteins and proinflammatory cytokines in hippocampal neuronal (HT22) and in microglial (BV2) cell lines treated with 1 µM Abo for 24 hours. A significant reduction in the MMP, cell viability and mRNA levels of Bcl2 and Il18 together with increased Il6 expression was observed in HT22 cells after Abo administration. CYM50308 and A971432 restored the Bcl2 mRNA level to control values (those of Abo-untreated cells) and pFTY720 markedly reduced the Il6 expression. In BV2 cells, Abo induced a significant decrease in the MMP, cell viability and expression of S1pr1, Bad, Bcl2, Tnf and Il18, which was not counteracted by any of the modulators used. In turn, mRNA levels of Il1b, Il6, were markedly increased in microglia after Abo treatment and the administration of studied compounds tended to exacerbate the proinflammatory effect of Abo. In conclusion, the toxic effect of Abo is more pronounced in microglia. S1P receptor modulators may to some extent mitigate proapoptotic and proinflammatory effects of Abo in HT22 cells. In contrast, the same compounds tend to enhance Abo-induced inflammatory changes in BV2 cells.

Introduction: Cancer stem cells (CSCs) are principal drivers in medulloblastoma (MB) initiation, growth, and progression. Our study aimed to explore the expression of CD133, CD44, and OCT4 signaling markers and their effects on the progression of MB.

Material and methods: A retrospective cohort analysis was conducted on brain tissue of 24 pediatric cases of MB from 2016-2020. Protein expression levels of CSC markers CD133, CD44, and OCT4 were evaluated immunohistochemically and their correlation with b-catenin activity was statistically analyzed.

Results: The mean age of patients was 10.2 years (range 3-17), with 18 (75%) males and 6 (25%) females. b-catenin was expressed in 20 (83.3%) tumors, and 4 (16.7%) tumors showed no expression. CD133 was minimally expressed in 6 (25%) tumors and 18 tumors (75%) showed no expression. CD44 was highly expressed in 6 (25%) tumors and 18 (75%) tumors showed minimal to no expression. OCT4 was expressed in all tumors. Despite MBs with positive b-catenin expression and absent CD133 expression having longer progression-free survival (PFS), this impact on PFS did not reach statistical significance ( p = 0.76). However, statistically significant differences in PFS were observed in MBs with positively expressed b-catenin and minimal or no CD44 expression, which showed prolonged PFS ( p = 0.0064). MB patients who did not express CD133 and received combined radiotherapy (RTx) and chemotherapy (CTx) showed longer PFS compared to MB patients with minimal CD133 expression. However, this association was statistically insignificant ( p = 0.42). The impact of CD44 expression and chemoradiation on PFS was statistically significant ( p = 0.0035). MB patients with absent or minimal CD44 expression who received RTx and CTx showed the longest PFS.

Conclusions: Medulloblastomas not expressing CSC markers (CD133, CD44) are associated with prolonged PFS and less resistance to chemoradiation. However, b-catenin is considered the main predictor for prognosis when compared to CSC markers.

Cytidine-5'-diphosphocholine (CDP-choline) is a key precursor for the intracellular synthesis of phosphatidylcholine and other phospholipids. Following either intravenous or oral application citicoline (CDP-choline of exogenous origin) undergoes quick decomposition to cytidine and choline, and for this reason it is frequently considered a prodrug. However, upon acute intravenous application in mice citicoline is, on a molar basis, 20 times less toxic than choline. To find out whether cytidine may attenuate toxicity of choline, in the present experiments we compared maximum tolerated doses of single intravenous injections of choline and equimolar mixture of choline and cytidine. We assumed that, if after oral intake a substantial part of citicoline is catabolised already in the intestine and its catabolites enter blood separately, intravenously applied equimolar mixture of cytidine and choline will be markedly less toxic than an equivalent molar dose of choline. However, the maximum tolerated single doses determined in our experiment for choline and equimolar mixture of choline and cytidine were similar. These data suggest that citicoline taken orally is not significantly decomposed in the intestinal lumen, but absorbed to blood as the intact molecule.

The neuroinflammation is a crucial component of virtually all neurodegenerative disorders, including Alzheimer's disease (AD). The bacterial lipopolysaccharide (LPS), a potent activator of the innate immune system, was suggested to influence or even trigger the neuropathological alterations in AD. LPS-induced neuroinflammation involves changes in transcription of several genes, thus controlling these molecular processes may be a potentially efficient strategy to attenuate the progression of AD. Since genome-wide association studies showed that the majority of AD-related genetic risk factors (AD-GRF) are connected to the immune system, our aim was to identify AD-GRF affected in the hippocampus by LPS-induced systemic inflammatory response (SIR). Moreover, we analysed the role of bromodomain and extraterminal domain (BET) proteins, the readers of the acetylation code, in controlling the transcription of selected AD-GRF in the brain during neuroinflammation. In our study, we used a mouse model of LPS-induced SIR and mouse microglial BV2 cells. JQ1 was used as an inhibitor of BET proteins. The level of mRNA was analysed using microarrays and qPCR. Our data demonstrated that among the established AD-GRF, only the expression of Cd33 was significantly upregulated in the hippocampus during SIR. In parallel, we observed an increase in the expression of Brd4, a BET family member. JQ1 prevented an LPS-evoked increase in Cd33 expression in the hippocampus of mice. Moreover, JQ1 reduced Cd33 expression in BV2 microglial cells stimulated with blood serum from LPS-treated mice. Our study suggests that LPS-evoked SIR may increase Cd33 gene expression in the brain, and inhibition of BET proteins through suppression of Cd33 expression could be a promising strategy in prevention or in slowing down the progression of neuroinflammation and may potentially affect the pathomechanism of AD.

Introduction: Ischemic stroke (IS) is a prevalent disease that poses a significant threat to human life and is responsible for a substantial financial burden. Research has established the crucial role of the miR-17-92 cluster in lung cancer, cardiovascular diseases, and traumatic brain injury. Despite this, few research studies had fully detected the potential of the miR-17-92 cluster as a novel circulating marker for diagnosing IS.

Material and methods: miR-17-92 cluster expression in IS was investigated using GSE117064 dataset via bioinformatics analysis. Moreover, qRT-PCR was conducted to further verify miR-17-92 cluster expression in 58 IS individuals and 50 healthy controls (HCs). These cluster members were examined regarding their potential for detecting and diagnosing IS using the ROC method.

Results: The expression level of serum miR-20a-5p, miR-19a-3p, miR-18a-5p, and miR-19b-3p was considerably lowered in IS in contrast with HC in both the GSE117064 cohort and clinical cohort. Moreover, these four miRNAs had a fair performance in IS detection. Thereafter, a diagnostic model based on these aforementioned four miRNAs was developed by logistic regression, which had an AUC of 0.974 in the ROC curve. This diagnostic module was verified using the GSE117064 dataset. Further analysis demonstrated an increasing level of the aforementioned miRNAs in day-7 IS patients compared with day-1 IS patients.

Conclusions: This research verified the downregulation of the miR-17-92 cluster in IS. This diagnostic model enrolling four cluster members may be a promising biomarker for IS detection.