We previously have revealed that 1-trifluoromethoxyphenyl-3-(1- propionylpiperidin-4-yl) urea (TPPU), as a soluble epoxide hydrolase (sEH) inhibitor can reduce infarct volume, protect blood-brain barrier (BBB) and brain against ischemic injury in rats. Here, we investigated the potential mechanisms of TPPU on BBB integrity in both in permanent middle cerebral artery occlusion (pMCAO) rat model and in oxygen-glucose deprivation/reperfusion (OGD/R)-induced human brain microvascular endothelial cells (HBMVECs) model. In pMCAO rat, TPPU administration decreased brain edema and Evans blue content, increased tight junction proteins (TJs) expression of claudin-5, occludin, and zonula occludens-1 (ZO-1). In OGD/R model, OGD/R significantly increased permeability and cell apoptosis, downregulated the expression of claudin-5, ZO-1, occludin, and lymphoma (Bcl)-2. Notably, TPPU pretreatment effectively protected the BBB integrity by reducing the permeability, promoting expression of claudin-5, ZO-1, occluding and Bcl-2, mitigating reactive oxygen species (ROS) injury and release of interleukin-1β (IL-1β), IL-6β, and tumor necrosis factor-α (TNF-α), downregulating expression of matrix metalloproteinase-9 (MMP-9), MMP-2, bcl-2-associated X protein (Bax), IL-1β, IL-6β, and TNF-α. Moreover, OGD/R induced the up-regulation of p-p65, p-IκB, and p-p38, which were effectively decreased after TPPU pretreatment in comparison with that of the OGD/R group. Furthermore, pyrrolidinedithiocarbamate (PDTC, a selective inhibitor of NF-κB p65) not only alleviated the OGD/R-induced HBMVECs injury and permeability, but also reduced the expression of TNF-α, IL-6, IL-1β, p-p65, and p-IκB, and the protective effect of PDTC was equivalent to that of TPPU. These results indicate that TPPU protects BBB integrity against ischemic injury by multiple protective mechanisms, at least in part, by reducing ROS, inflammation, apoptosis, and suppressing the nuclear factor-κB (NF-κB) and p38 signaling pathways.

Objective: This investigation aimed at studying the prevalence of cerebral microbleeds (CMBs), including risk factors and the correlation of CMBs to ischemic stroke (IS) patient end results.Methods: Four hundred and fifty-nine acute IS cases were recruited between April 2014 and December 2016. Cerebral microbleeds were analyzed using susceptibility-weighted imaging (SWI) brain MRI scan. The enrolled patients with acute IS were followed up for 12–24 months, with a median follow-up time of 19 months. The follow-up endpoint events including recurrent ischemic stroke (RIS), intracranial hemorrhage (ICH), transient ischemic attack (TIA), mortality, and cardiovascular events. The associations between vascular risk factors and CMBs in IS patients were analyzed using univariate and multivariate logistic regression analysis. Cox regression model was employed for evaluating CMB impact on clinical outcome.Results: Among 459 enrolled patients, 187 (40.7%) had CMBs and 272 (59.2%) had no CMB. In comparison with patients with no CMBs, age was higher and hypertension was more frequent in patients with CMBs. Multivariate logistic regression analyses revealed age and hypertension were independently associated with the presence of CMBs. Among the patient cohort, 450 cases completed the follow-up. During the follow-up period, 22 (4.9%) of patients developed ICH, 12 (2.7%) developed TIA, 68 (15.1%) developed RIS, cardiovascular events occurred in 20 (4.44%), and 13 (2.89%) cases were mortalities. Compared with patients without CMBs, IS patients with CMBs have an increased prevalence of ICH (p < 0.05). However, no statistically valid variations regarding other outcome incidences between both groups was identified (p > 0.05). The incidence of ICH was elevated in tandem with elevations in number of CMBs. Following adjusting for age, multivariate Cox proportional-hazards regression analysis revealed that CMBs ≥10 were independent predictors of ICH in acute IS patients.Conclusion: Age and hypertension are independently associated with the presence of CMBs. Intracranial hemorrhage incidence rate was increased with the number of CMBs, and the number of CMBs ≥10 were independent predictors of ICH in acute stroke patients.

Mortality is the most clinically serious outcome, and its prevention remains a constant struggle. This study was to assess whether intravenous or oral vitamin C (Vit-C) therapy is related to reduced mortality in adults. Data from Medline, Embase, and the Cochrane Central Register databases were acquired from their inception to 26 October 2022. All randomized controlled trials (RCTs) involving intravenous or oral Vit-C against a placebo or no therapy for mortality were selected. The primary outcome was all-cause mortality. Secondary outcomes were sepsis, COVID-19, cardiac surgery, noncardiac surgery, cancer, and other mortalities. Forty-four trials with 26540 participants were selected. Although a substantial statistical difference was observed in all-cause mortality between the control and the Vit-C-supplemented groups (p = 0.009, RR 0.87, 95% CI 0.78 to 0.97, I2 = 36%), the result was not validated by sequential trial analysis. In the subgroup analysis, mortality was markedly reduced in Vit-C trials with the sepsis patients (p = 0.005, RR 0.74, 95% CI 0.59 to 0.91, I2 = 47%), and this result was confirmed by trial sequential analysis. In addition, a substantial statistical difference was revealed in COVID-19 patient mortality between the Vit-C monotherapy and the control groups (p = 0.03, RR 0.84, 95% CI 0.72 to 0.98, I2 = 0%). However, the trial sequential analysis suggested the need for more trials to confirm its efficacy. Overall, Vit-C monotherapy does decrease the risk of death by sepsis by 26%. To confirm Vit-C is associated with reduced COVID-19 mortality, additional clinical random control trials are required.

With the advancement of technology, increasingly many newborns are receiving general anesthesia at a young age for surgery, other interventions, or clinical assessment. Anesthetics cause neurotoxicity and apoptosis of nerve cells, leading to memory and cognitive impairments. The most frequently used anesthetic in infants is sevoflurane; however, it has the potential to be neurotoxic. A single, short bout of sevoflurane exposure has little impact on cognitive function, but prolonged or recurrent exposure to general anesthetics can impair memory and cognitive function. However, the mechanisms underlying this association remain unknown. Posttranslational modifications (PTMs), which can be described roughly as the regulation of gene expression, protein activity, and protein function, have sparked enormous interest in neuroscience. Posttranslational modifications are a critical mechanism mediating anesthesia-induced long-term modifications in gene transcription and protein functional deficits in memory and cognition in children, according to a growing body of studies in recent years. Based on these recent findings, our paper reviews the effects of sevoflurane on memory loss and cognitive impairment, discusses how posttranslational modifications mechanisms can contribute to sevoflurane-induced neurotoxicity, and provides new insights into the prevention of sevoflurane-induced memory and cognitive impairments.