Folia neuropathologica最新文献

Introduction: The present study explored the effects and possible mechanisms of ZDHHC16 in a model of cerebral apoplexy (CA).

Material and methods: Patients with CA were collected from our hospital. Mice were used to establish an middle cerebral artery occlusion (MCAO) model.

Results: ZDHHC16 levels in patients with CA were up-regulated. ZDHHC16 up-regulation promoted inflammation and accelerated mitochondrial damage in the in vitro model. ZDHHC16 gene up-regulation promoted ferroptosis of neurocytes. The inhibition of ZDHHC16 prevented cerebral apoplexy in the mouse model. ZDHHC16 up-regulation suppressed CREB through interlinkage of CREB by promoting CREB ubiquitination. CREB agonists inhibited the effects of ZDHHC16 up-regulation in the in vitro model. CREB inhibitor inhibited the effects of ZDHHC16 down-regulation in the in vitro model.

Conclusions: We conclude that ZDHHC16 promoted ferroptosis and inflammation in a model of CA through the suppression of CREB. The findings might be of benefit in the treatment of CA or other nervous system diseases.

Sevoflurane is an inhalation anaesthetic agent widely used in clinical settings. Despite good surgical outcomes using sevoflurane, patients frequently develop postoperative cognitive dysfunction (POCD). An enriched environment (EE), as a rehabilitation technique, could provide objects and tools to facilitate neuromotor and visual stimuli and brain activity, and is reported to improve cognitive functions. We aim to investigate the impairments of sevoflurane inhalation on cognitive function in mice and determine the benefits of EE in ameliorating POCD. Eighteen-month-old mice were exposed to sevoflurane inhalation for 2 h and then placed in standard environment (SE) or EE cages. The mice without sevoflurane exposure in standard or EE cages were used as controls. The behavioural tests include Morris water maze, Y maze and novel object recognition. Magnetic resonance imaging (MRI) was used to determine the blood circulation in the brains. The proangiogenic factors (CD31, angiopoietin-1, vascular endothelial growth factor, and N-cadherin) and neurotrophic (brain-derived neurotrophic factor, post-synaptic density protein 95) expression in hippocampus of aged mice were evaluated by Western blotting and RT-PCR analysis. Sevoflurane-exposed mice demonstrated reduced performance in learning, memory and spatial memory tests. Enriched environment improved the behavioural performance of sevoflurane-exposed animals. Sevoflurane exposure reduced the blood flow in the brains, and these effects were ameliorated by EE habitation. The EE also promoted the expression of angiogenic and neurotropic factors in sevoflurane-exposed animals. In summary, EE is effective in ameliorating the side-effects of sevoflurane exposure in aged mice.

Introduction: Intracranial hemorrhage (ICH) in functional neurosurgery is a relatively rare but serious complication. One of the possible risk factors related to ICH is the number of trajectories made for microelectrode recording (MER). Authors who solely rely on macrostimulation using macroelectrodes argue that the incidence of ICH is much lower while maintaining good clinical efficacy of deep brain stimulation (DBS). The present study aimed to assess the incidence of ICH in DBS procedures by reducing to the minimum the number of brain passes and the diameter of guiding cannulas. For this reason, we used one MER guiding cannula exclusively for track making with subsequent macrostimulation done through the implanted DBS electrode.

Material and methods: All DBS procedures performed between January 2018 and January 2022 in the Department of Neurosurgery of the Institute of Psychiatry and Neurology in Warsaw were analyzed for possible ICH and other perioperative complications. The DBS lead was implanted by an MR image-guided and intraprocedural CT-verified approach. No MER was done.

Results: During four years 191 patients underwent 267 DBS lead implantations in 252 stereotactic procedures. ICH occurred in 2 patients. Both were symptomatic. Adverse symptoms resolved within a week. Two DBS leads required replacement. There was 1 case of hematoma at the implantable pulse generator (IPG) site and 1 case of pneumothorax due to tunneling of the extension.

Conclusions: Our surgical technique has a low incidence of ICH. Symptomatic ICH affected 2 patients. The other perioperative complications mentioned above required repeated surgery or conservative treatment. No patient suffered from permanent deficits.

Cerebral ischemia/reperfusion causes high disability, recurrence, and mortality. Ischemic stroke is a powerful stimulus that triggers significant microglia activation. Ginsenoside Rb1 (GS-Rb1) has been demonstrated to have neuroprotective effects in the central nervous system. In this study, the effects of GS-Rb1 against cerebral ischemia/reperfusion were explored. A mouse model of middle cerebral artery occlusion (MCAO) was used to mimic the cerebral ischemia/reperfusion. Mice in MCAO + GS-Rb1 groups received 5, 10, or 20 mg/kg GS-Rb1 through intraperitoneal injection. Modified neurological severity scoring (mNSS) showed neurological function, while the open field test tested the anxiety-like behaviors. Cognitive impairment was evaluated by Morris water maze. Protein levels were evaluated by ELISA and Western blot and mRNA levels were analyzed by qRT-PCR. When compared to the MCAO mice, mice in the MCAO + GS-Rb1 group had significantly lower mNSS scores and less brain water content. GS-Rb1 alleviated both cognitive impairment and anxiety and inhibited microglial activation in the cerebral ischemia/reperfusion model. GS-Rb1 enhanced M2-type microglia polarization while inhibiting M1-type microglia polarization. In summary, we observed that GS-Rb1 had neuro-protective effects in a cerebral ischemia/reperfusion mouse model through regulating the microglia polarization.

Introduction: The incidence of major depressive disorder (MDD) in adults has been associated with dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, leading to elevated secretion of cortisol. However, limited research has been done globally on how the dysregulated HPA axis and changed cortisol levels relate to depression in adolescents and young adults. The objective of this research was to conduct a systematic review and meta-analysis of the association between cortisol level, a marker of HPA axis activity, and depression in adolescents and young adults.

Material and methods: A systematic search was conducted using four electronic databases (PubMed, EMBASE, Scopus, and Cochrane Library) to select publications published in peer-reviewed journals written in English. The odds ratio (OR) and standard mean difference (SMD) were calculated, along with their 95% confidence intervals. We assessed heterogeneity using Cochrane c2 and I2 statistics and the appropriate P-value. The analysis used RevMan 5.3.

Results: The current meta-analysis included 10 cross-sectional studies with a total of 1301 adolescents and young adults across various age cohorts, with 629 depressed and 672 non-depressed individuals. It was found that the likelihood of depression is higher among the included adolescents and young adults, with an OR of 1.62 (95% CI: 0.44-5.92), and depressed individuals have significantly higher cortisol levels (SMD of 0.87 (95% CI 0.43-1.31) and cortisol stress response SMD of 0.68 (95% CI 0.31-1.05)). Furthermore, there was a strong positive linear association ( r = 0.82) between morning and afternoon cortisol levels in adolescents and young adults and depression scores.

Conclusions: The results of our study indicate that an increase in both morning and afternoon cortisol levels is associated with the development of depression in adolescence and young adults. Research has indicated that an increased level of cortisol is considered a risk factor for depression during adolescence and a linear correlation exists between cortisol levels and depression scores.

Activation of the NogoA/NgR/ROCK pathway limits nerve repair after brain ischemia-reperfusion (I/R) injury. Triptolide displays anti-inflammatory, anti-oxidant, and immunosuppressive effects and is derived from the traditional Chinese medicine Tripterygium wilfordii Hook F. This agent can also penetrate the blood-brain barrier, where it has a neuroprotective effect and ameliorates cerebral I/R injury via an as yet unknown mechanism(s). Here, an animal model of middle cerebral artery occlusion and reperfusion (MCAO/R) was employed to assess triptolide's therapeutic impact on brain I/R injury and the possible mechanism of action. The results indicate that triptolide treatment can decrease cerebral infarction and nerve injury after cerebral I/R injury. Importantly, in vivo and in vitro experiments revealed that treatment with triptolide decreased NogoA, NgR, p75NTR and ROCK2 expression, and upregulated the expression of GAP43 and PSD-95, thus suggesting improved synaptic function. These results indicate that triptolide can promote nerve repair following brain I/R injury by inhibiting NogoA/NgR/ROCK signalling.

Introduction: MicroRNA (miR)-485-5p has been linked to regulation of neurological disorders. The current study examined miR-485-5p levels in patients with epilepsy secondary to cerebral infarction and investigated its predictive significance.

Material and methods: The Gene Expression Omnibus (GEO) database was employed to screen differentially expressed miRNAs in cerebral infarction and epilepsy. 168 patients with cerebral infarction were enrolled, including 67 patients with secondary epilepsy and 101 patients without secondary epilepsy. Serum miR-485-5p levels were examined by reverse transcription-quantitative real-time PCR (RT-qPCR). Logistic regression analysis was used to explore risk factors for epilepsy secondary to cerebral infarction. The diagnostic and predictive value of miR-485-5p was evaluated by receiver operating characteristic (ROC) analysis. Bioinformatics predicted miR-485-5p target mRNA and performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis.

Results: The GEO database identified differentially expressed miRNAs including miR-485-5p. miR-485-5p levels were poorly expressed in patients with cerebral infarction ( p < 0.05) and negatively correlated with the National Institutes of Health Stroke Scale (NIHSS) score, an indicator of cerebral infarction severity. Additionally, miR-485-5p is a typical indicator for differentiating cerebral infarctions from controls. Serum miR-485-5p was lower in patients with epilepsy secondary to cerebral ischemia compared to non-epilepsy patients and is a potential risk factor for epilepsy secondary to cerebral infarction. The sensitivity and specificity for predicting epilepsy were 74.63% and 80.20%, respectively. KEGG pathway studies revealed miR-485-5p's target mRNA is primarily enriched in the adipocytokine signaling pathway and the AMPK pathway.

Conclusions: miR-485-5p correlates with cerebral infarction severity. Low expression of miR-485-5p is a promising predictive biomarker for epilepsy secondary to cerebral infarction.

Clear cell meningioma (CCM) is a rare subtype of meningioma, especially unusual as a neoplasm of the filum terminale. Clear cell meningioma seems to have a more aggressive nature and a higher risk of recurrence than WHO grade I meningiomas. A 44-year-old woman presented with lower back pain radiating to the left leg and mild weakness in the left leg. Magnetic resonance imaging (MRI) showed a well-demarcated, intradural lesion filling the spinal canal at the L3-S1 levels and compressing the cauda equina. The patient underwent laminectomy from L3 to S1. During the operation, the filum terminale was identified as a structure that was disappearing into the tumor. The filum terminale was cut and the tumor was totally removed in one piece. Pathological findings were indicative of the diagnosis of clear cell meningioma, CNS WHO G2. Postoperative magnetic resonance imaging at 6 months showed no residual mass. Total surgical excision of the CCM of the spinal cord should be chosen as the optimal treatment. In addition, radiological follow-up is equally important due to the high risk of recurrence. Our case is unusual in that the tumor's location was the filum terminale.

Introduction: Glioma is one of the most commonly tumours which occurs in the central nervous system and accounts for nearly 80% of brain tumours, with a significantly high mortality and morbidity. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are used as EGFR targeted therapy in various types of solid tumours; however, effective treatment for glioma is still limited. Osimertinib is an irreversible, oral third-generation TKI that targets the mutation at T790M, which causes cancer cells to acquire resistance to drugs. Osimertinib could be effective in the treatment of EGFR mutations with minimal effects on the activity of wild-type EGFR. Absent in melanoma 2 (AIM2) is highly expressed in glioma cells, promoting the maturation of pro-cancer cytokines and contributing to progression of glioma. However, the secretion of pro-cancer cytokines of tumour cells has been regarded as the resistance mechanism to EGFR-TKIs, including osimertinib. A high level of these cytokines also indicates a shorter progression-free survival (PFS). As AIM2 regulates the secretion of pro-cancer cytokines, we thought inhibition of AIM2 may contribute to the therapeutic effect of EGFR-TKIs.

Material and methods: We first established AIM2 inhibition and overexpression in cells. Then, the viability rate of cells was calculated by cell counting kit-8 (CCK-8) method, and apoptotic ratio of cells were measured by flow cytometry. The expression of inflammatory-related genes was detected using quantitative polymerase chain reaction (qPCR), concentrations of inflammatory-related factors were measured using enzyme-linked immunosorbent assay (ELISA). The expression of Wnt/b-catenin and EGFR/Ras/Mitogen-activated protein kinase kinase 1 (MEK) signalling pathway components was detected using western blotting.

Results: We found that inhibition of AIM2 enlarged the effect of osimertinib on the upregulation of inflammatory gene expression and secretion of these genes, increasing apoptosis. In addition, we also found that AIM2 could enhance the effect of osimertinib on reducing the expression of the Wnt/b-catenin and EGFR/Ras/MEK signalling pathways, resulting in the inhibition of cellular proliferation, and exerting an anti-tumour effect. These effects were also observed using in vivo experiments.

Conclusions: AIM2 presents a potential therapeutic target in treatment of glioma.

Introduction: The objective of this study was to investigate the expression of serum miR-7 and erythrocyte sedimentation rate (ESR) levels in patients with acute herpes zoster (HZ) and their evaluation value for postherpetic neuralgia (PHN).

Material and methods: A total of 98 patients with acute HZ and 97 healthy people were enrolled in this study. The levels of miR-7 and ESR were analyzed in patients with HZ and healthy people. According to whether PHN occurred within 3 months after lesion regression, the patients were divided into HZ patients with PHN and HZ patients without PHN, and the levels of miR-7 and ESR of the two groups were analyzed. The clinical indicators of the PHN and non-PHN groups were analyzed by univariate and multivariate analysis, and the risk factors affecting PHN were evaluated. ROC curves were established to evaluate the diagnostic value of miR-7 and ESR in PHN.

Results: Compared with the healthy control group, miR-7 and ESR levels of patients with HZ showed a significant downward and upward trend, respectively. Compared with the patients without PHN, patients with PHN had decreased miR-7 and increased ESR. MiR-7 and ESR were significantly correlated with clinical indicators such as VAS scores in patients with HZ. Multivariate logistic regression analysis showed that miR-7 and ESR were independent factors influencing the occurrence of PHN. ROC analysis revealed that the combination of miR-7 and ESR had high clinical diagnostic accuracy for PHN.

Conclusions: The reduction of miR-7 and the increase of ESR are independent risk factors for PHN in HZ patients, and the ROC curve constructed based on the clinical expression levels of miR-7 and ESR showed high clinical diagnostic value for PHN.