Exosomal microRNAs: implications in the pathogenesis and clinical applications of subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH) is a severe acute neurological disorder with a high fatality rate. Early brain injury (EBI) and cerebral vasospasm are two critical complications of SAH that significantly contribute to poor prognosis. Currently, surgical intervention and interventional therapy are the main treatment options for SAH, but their effectiveness is limited. Exosomes, which are a type of extracellular vesicles, play a crucial role in intercellular communication and have been extensively studied in the past decade due to their potential influence on disease progression, diagnosis, and treatment. As one of the most important components of exosomes, miRNA plays both direct and indirect roles in affecting disease progression. Previous research has found that exosomal miRNA is involved in the development of various diseases, such as tumors, chronic hepatitis, atherosclerosis, diabetes, and SAH. This review focuses on exploring the impact of exosomal miRNA on SAH, including its influence on neuronal apoptosis, inflammatory response, and immune activation following SAH. Furthermore, this review highlights the potential clinical applications of exosomal miRNA in the treatment of SAH. Although current research on this topic is limited and the clinical application of exosomal miRNA has inherent limitations, we aim to provide a concise summary of existing research progress and offer new insights for future research directions and trends in this field.

Mesenchymal stem cell-derived extracellular vesicles/exosome: A promising therapeutic strategy for intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) is the second largest type of stroke with high mortality and morbidity. The vast majority of survivors suffer from serious neurological defects. Despite the well-established etiology and diagnose, there is still some controversy over the ideal treatment strategy. MSC-based therapy has become an attractive and promising strategy for the treatment of ICH through immune regulation and tissue regeneration. However, accumulating studies have revealed that MSC-based therapeutic effects are mainly attributed to the paracrine properties of MSC, especially small extracellular vesicles/exosome (EVs/exo) which are considered to be the key mediators of the protective efficacy from MSCs. Moreover, some papers reported that MSC-EVs/exo have better therapeutic effects than MSCs. Therefore, EVs/exo has become a new choice for the treatment of ICH stroke in recent years. In this review, we mainly concentrate on the current research progress on the use of MSC-EVs/exo in the treatment of ICH and the existing challenges in their transplation from lab to clinical practice.

Surgery and antibiotics for the treatment of lupus nephritis with cerebral abscesses: A case report.

BACKGROUND: Systemic lupus erythematosus (SLE) patients are extremely susceptible to opportunistic infections due to glucocorticoid and immunosuppressive treatments, which often occur in the respiratory system, the urinary system and the skin. However, multiple cerebral infections are rarely reported and their treatment is not standardized, especially when induced by a rare pathogen. CASE SUMMARY: A 46-year-old woman was treated with glucocorticoid and immunosuppressant for SLE involving the hematologic system and kidneys (class IV-G lupus nephritis) for more than one year. She was admitted to hospital due to headache and fever, and was diagnosed with multiple cerebral abscesses. Brain enhanced magnetic resonance imaging showed multiple nodular abnormal signals in both frontal lobes, left parietal and temporal lobes, left masseteric space (left temporalis and masseter region). The initial surgical plan was only to remove the large abscesses in the left parietal lobe and right frontal lobe. After surgery, based on the drug susceptibility test results (a rare pathogen Nocardia asteroides was found) and taking into consideration the patient's renal dysfunction, a multi-antibiotic regimen was selected for the treatment. The immunosuppressant mycophenolate mofetil was discontinued on admission and the dose of prednisone was reduced from 20 mg/d to 10 mg/d. Re-examination at 3 mo post-surgery showed that the intracranial lesions were reduced, the edema around the lesions was absorbed and dissipated, and her neurological symptoms had disappeared. The patient had no headaches or other neurological symptoms and lupus nephritis was stable during the 2-year follow-up period. CONCLUSION: In this report, we provide reasonable indications for immunosuppression, anti-infective therapy and individualized surgery for an SLE patient complicated with multiple cerebral abscesses caused by a rare pathogen, which may help improve the diagnosis and treatment of similar cases.

Identification of key modules and hub genes in glioblastoma multiforme based on co-expression network analysis.

Glioblastoma multiforme (GBM) is the most malignant primary tumour in the central nervous system, but the molecular mechanisms underlying its pathogenesis remain unclear. In this study, data set GSE50161 was used to construct a co-expression network for weighted gene co-expression network analysis. Two modules (dubbed brown and turquoise) were found to have the strongest correlation with GBM. Functional enrichment analysis indicated that the brown module was involved in the cell cycle, DNA replication, and pyrimidine metabolism. The turquoise module was primarily related to circadian rhythm entrainment, glutamatergic synapses, and axonal guidance. Hub genes were screened by survival analysis using The Cancer Genome Atlas and Human Protein Atlas databases and further tested using the GSE4290 and Gene Expression Profiling Interactive Analysis databases. The eight hub genes (NUSAP1, SHCBP1, KNL1, SULT4A1, SLC12A5, NUF2, NAPB, and GARNL3) were verified at both the transcriptional and translational levels, and these gene expression levels were significant based on the World Health Organization classification system. These hub genes may be potential biomarkers and therapeutic targets for the accurate diagnosis and management of GBM.

Targeting CCL20 inhibits subarachnoid hemorrhage-related neuroinflammation in mice.

Recent evidence suggests that CC chemokine ligand 20 (CCL20) is upregulated after subarachnoid hemorrhage (SAH). Here, we investigated the functions of CCL20 in SAH injury and its underlying mechanisms of action. We found that CCL20 is upregulated in an SAH mouse model and in cultured primary microglia and neurons. CCL20-neutralizing antibody alleviated SAH-induced neurological deficits, decreased brain water content and neuronal apoptosis, and repressed microglial activation. We observed increased levels of CCL20, CC chemokine receptor 6 (CCR6), interleukin 1 beta (IL-1ß), and tumor necrosis factor alpha (TNF-α), as well as of microglial activation in microglia treated with oxyhemoglobin (OxyHb). CCL20 or CCR6 knockdown reversed the effects of OxyHb on microglia. Conditioned medium from OxyHb-treated microglia induced neuronal apoptosis, while the percentage of apoptotic neurons in the conditioned medium from microglia transfected with CCL20 siRNA or CCR6 siRNA was decreased. We observed no decrease in OxyHb-induced apoptosis in CCL20-knockdown neurons. Conditioned medium from OxyHb-treated neurons led to microglial activation and induced CCR6, IL-1ß and TNF-α expression, while CCL20 knockdown in neurons or CCR6 knockdown in microglia reversed those effects. Our results thus suggest CCL20 may be targeted to elicit therapeutic benefits after SAH injury.

Computerized Tomography Radiomics Features Analysis for Evaluation of Perihematomal Edema in Basal Ganglia Hemorrhage.

To evaluate the edema area around basal ganglia hemorrhage by the application of computerized tomography (CT)-based radiomics as a prognostic factor and improve the diagnosis efficacy, a total of 120 patients with basal ganglia hemorrhage were analyzed retrospectively. The texture analysis software Mazda 3.3 was used to preprocess the CT images and manually sketch the region of interest to extract the texture features. The extracted texture features were selected by Fisher coefficient, POE+ACC and mutual information. The texture discriminant analysis uses the B11 module in the Mazda 3.3 software. The data were randomly divided into a training dataset (67%) and test dataset (33%). To further study the texture features, the training dataset can be divided into groups according to the median of GCS score, NIHSS score, and maximum diameter of hematoma. Random forest model, support vector machine model, and neural network model were built. AUC of the receiver operating characteristics curve was used to assess the performance of models with test dataset. Among all texture post-processing methods, the lowest error rate was 2.22% for the POE+ACC/nonlinear discriminant. For the maximum diameter of hematoma, GCS score, and NIHSS score group, the lowest error rate were 26.66%, 23.33%, and 30.00%, respectively. The values of AUCs were 0.87, 0.81, and 0.76, for random forest model, support vector machine model, and neural network model in the test dataset, respectively. Radiomic method with proper model may have a potential role in predicting the edema area around basal ganglia hemorrhage. It can be used as a secondary group in the diagnosis of edema area around basal ganglia hemorrhage.