Neuroprotective effects of Chrysanthemum morifolium on cerebral ischemia- reperfusion injury contributes to the oxidative stress suppression and related Keap1/Nrf2 pathway.

BACKGROUND: Ischemic stroke, the cause of death and disability worldwide, is closely related to oxidative stress damage. Chrysanthemum has profound antiantioxidant activity. We aimed to verify whether Chrysanthemum morifolium extract (CME) influences brain injury in cerebral ischemia-reperfusion injury (CR/RI) model. METHODS: In vitro, rat hippocampal H19-7 neurons were pretreated with CME, CR/RI was simulated with oxygen glucose deprivation/reoxygenation (OGD/R). The cell viability, apoptosis, lactate dehydrogenase release, reactive oxygen species (ROS) generation, malonaldehyde (MDA) content and superoxide dismutase（SOD） activity were detected. In vivo, middle cerebral artery occlusion (MCAO) model rats were pre-administered with CME, and then behavioral test, triphenyltetrazolium chloride (TTC), hematoxylin-eosin staining (HE), terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL), ROS immunofluorescence, MDA and SOD activity were tested. Furthermore, Keap1/Nrf2 signaling of CME in CI/RI was investigated. RESULTS: In OGD/R induced in H19-7 cells, CME increased OGD/R-induced cell viability and reduced cell apoptosis, which was reversed by siNrf2 transfection . In MCAO rats, CME improved the neurological deficits and alleviated brain injury. However, co-treatment with MLK385 counteracted these neuroprotective effects of CME on MCAO rats. CONCLUSION: CME could significantly reduce oxidative stress and nerve injury in vitro and in vivo models of CI/RI by regulating the Keap1/Nrf2 pathway.

Hypertonic Saline Alleviates Brain Edema After Traumatic Brain Injury via Downregulation of Aquaporin 4 in Rats.

BACKGROUND Hypertonic saline (HS) has been successfully used for treatment of various forms of brain edema. Decreased expression of aquaporin (AQP)4 and pro-inflammatory cytokines such as tumor necrosis factor (TNF)-a and interleukin (IL)-1b have been linked to edema pathogenesis. This study examined the effect of 3% HS on brain edema in a rat model of traumatic brain injury (TBI). MATERIAL AND METHODS Sprague-Dawley rats were subjected to TBI induced by a controlled cortical impactor. The HS group was injected with 3% NaCl until the end of the study period. AQP4, TNF-α, IL-1ß, and caspase-3 levels were measured by Western blotting, immunohistochemistry, enzyme-linked immunosorbent assay, and quantitative real-time PCR. Brain water content was also measured. Apoptotic cells in brain tissue were detected with terminal deoxynucleotidyl transferase dUTP nick-end labeling. Brain water content decreased following treatment with 3% HS relative to the TBI group. RESULTS This was accompanied by decreases in AQP4, TNF-α, and IL-1ß mRNA and protein levels. TBI resulted in increases in caspase-3 mRNA expression and the number of apoptotic cells; treatment with 3% HS suppressed apoptosis as compared to the TBI group. CONCLUSIONS Treatment with 3% HS ameliorated TBI-induced brain edema, possibly by suppressing brain edema, pro-inflammatory cytokine expression, and apoptosis.

Clinical independent prognostic factors and overall survival prognostic nomogram for intracranial subependymoma: A SEER population-based analysis 2004-2016.

Purpose: This study was launched to ascertain the independent prognostic factors influencing the overall survival (OS) prognosis of intracranial subependymoma and construct a prognostic model to predict OS time. Materials and methods: We collected data from patients with intracranial subependymoma, including treatment data, follow-up data, and clinical and pathological characteristics from the SEER database within 2004 to 2016, and patients were randomly classified into training and validation cohorts. Univariate and multivariate analyses were applied to the training group through building a Cox proportional hazards model. According to the results of multivariate analysis, we established a nomogram to forecast the OS rate of the per-case patient graphically, then calculated the accuracy of verification in both training and validation cohorts by concordance index (C-index). Univariate and multivariate analyses were used for different subgroups of unoperated versus operated, gross total resection (GTR), subtotal resection (STR), and biopsy after using the propensity score matching (PSM) analyses. Results: A total of 667 patients were enrolled, and we randomly assigned 535 patients (80.21%) into the training cohort and 132 patients (19.79%) into the validation cohort. Age [hazard ratio (HR) = 6.355; 95% confidence interval (CI), 2.240-18.029; p = 0.001] and sex (HR = 0.475; 95% CI, 0.232-0.974; p = 0.042) were the independent prognostic factors in the training cohort. On the basis of age and sex, the nomogram was established to predict the OS for every patient (C-index = 0.733 ± 0.065 in the training cohort and 0.850 ± 0.065 in the validation cohort), and calibration plots reflected the reliability of the nomogram. Age, gender, or laterality was the independent prognostic factor for OS in the different matched subgroups of unoperated versus operated, GTR, STR, and biopsy. Surgical treatment, race, year of diagnosis, insurance, tumor location, tumor size, pathology, tumor grade, and radiation were not statistically significantly different in OS for subependymoma in our research. Conclusion: Age and sex were the independent prognostic variables for OS in intracranial subependymoma. According to our research, we should not be more inclined to choose conservative or surgical treatment. Nonetheless, the information that we present might be useful to suggest potential hypotheses to be tested in the clinical research setting.

Clinical prognostic factors for central neurocytoma and subgroup analysis of different treatment measures: A SEER database-based retrospective analysis from 2003 to 2019.

Purpose: The study aimed to identify clinical prognostic factors affecting overall survival (OS) in patients with central neurocytoma (CN) and to determine independent prognostic factors in the subgroups of different treatment modalities using a retrospective analysis based on the SEER database from 2003 to 2019. Materials and methods: Data regarding patients with CN, including basic clinical characteristics, treatment measures, and prognosis follow-up, were extracted from the SEER database. The prognostic variables for all patients were assessed using log-rank test as well as univariate and multivariate analyses based on the Cox proportional hazards model. The same statistical methods were used for analysis in different subgroups of gross total resection (GTR), subtotal resection (STR), no surgery, radiotherapy (RT), and no RT. Results: In total, 413 patients were enrolled in this study. Tumor size, primary site surgery, and RT were independent prognostic factors in all patients with CN. In subgroup analyses, RT was not an independent prognostic factor in patients with GTR. However, sex and race were independent prognostic factors in patients with STR. Additionally, tumor size was an independent prognostic factor in patients who did not undergo surgery. Furthermore, sex and primary site were independent prognostic factors in patients who received RT. Size and primary site surgery were independent prognostic factors in patients without RT. Conclusion: In our study, patients with small tumors or GTR or those who did not receive RT showed a better prognosis. GTR was the preferred treatment for CN. RT was not recommended for patients after GTR. Men and African American showed certain advantages after STR surgery. Tumors with a size of >4 cm were recommended for active treatment. In the RT subgroup, patients with tumors outside the ventricle or women had a poorer prognosis than those with tumors within the ventricle or men, respectively. These findings will help clinicians and patients understand the treatment and prognosis of CN visually and intuitively.