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Neuroinflammation contributes to the progression of cerebral ischemia/reperfusion (I/R) damage. Scutellarin (SL) is a glucuronide flavonoid that has apoptotic, anti‐inflammatory, and anti‐tumor properties. It is anti‐oxidant and anti‐inflammatory mechanism as a neuroprotective against ischemic brain injury is unknown. The purpose of the study was to examine the role and mechanism of SL in preventing I/R damage in a rat model. SL (40 and 80 mg/kg) was given to the rats for 14 days before the ischemic stroke. SL administration prevented I/R mediated brain injury, and neuronal apoptosis. Malondialdehyde, superoxide dismutase, glutathione, IL‐6, and IL‐1β and nitric oxide were modulated by SL. SL suppressed the p65 and p38 expressions in particular. The findings show that SL protects rats from cerebral damage caused by I/R through the nuclear factor kappa‐B p65 and p38 mitogen‐activated protein kinase signaling pathway. Thus, SL protected the brain of rats from ischemic injury by inhibiting the inflammatory process. [ABSTRACT FROM AUTHOR]

Abstract With the speedy technological advances during the past few decades, human exposure to the electromagnetic field (EMF) has become increasingly common. Exposure to EMF may induce neural injuries and dysfunction of various organs, likely involving neuroinflammation and activation of microglial cells. Isoflurane preconditioning (IP) is shown to provide neuroprotection in various neurological diseases by inhibiting excessive neuroinflammatory responses. Brain samples harvested from rats exposed to electromagnetic pulse (EMP) with or without IP were subjected to qPCR, Western blot assay, and immunohistochemistry to determine the expression of pro-inflammatory/anti-inflammatory microglia markers and a variety of pro- and anti-inflammatory mediators. Suppressor of cytokine signaling 1 (SOCS1) siRNA was used in cultured N9 microglia cells to examine the roles of SOCS1 in the effect of IP. In both in vivo and in vitro experiments, EMP-exposed microglia were predominantly pro-inflammatory microglia, accompanied by increased expression of pro-inflammatory cytokines and chemokines, and activation of TLR4 pathway, leading to neuronal death. IP reversed the changes induced by EMP and switched the activated microglia to an anti-inflammatory phenotype. SOCS1 siRNA abolished the beneficial effects of IP. IP ameliorates EMP-induced neural injuries by shifting microglia polarization from pro-inflammatory to anti-inflammatory phenotype via upregulation of SOCS1. Highlights • SOCS1 siRNA abolishes the beneficial effects of IP. • IP ameliorates EMP-induced neural injuries. • IP shifts microglia polarization from pro-inflammatory to anti-inflammatory phenotype via upregulation of SOCS1. [ABSTRACT FROM AUTHOR]

• miR-665-3p was decreased by OGD in microglial cells. • miR-665-3p attenuated OGD-induced microglial apoptosis and inflammation. • TRIM8 was identified as a target gene of miR-655-3p. • miR-655-3p inhibited NF-κB activation by targeting TRIM8. Microglial inflammation induced by ischemic stroke aggravates brain damage. MicroRNAs (miRNAs) have emerged as pivotal regulators in ischemic stroke-induced inflammation in microglial cells. miR-665-3p has been reported as a critical inflammation-associated miRNA. However, whether miR-665-3p participates in regulating microglial inflammation during ischemic stroke is underdetermined. This study investigated the potential role of miR-665-3p in stroke-induced inflammation in microglial cells using a cellular model of oxygen-glucose deprivation (OGD)-stimulated microglial cells in vitro. We found that miR-665-3p expression was decreased in microglial cells exposed to OGD treatment. Functional experiments demonstrated that the overexpression of miR-665-3p attenuated OGD-induced apoptosis and inflammation in microglial cells. Notably, tripartite motif 8 (TRIM8) was identified as a target gene of miR-665-3p. TRIM8 expression was induced by OGD treatment in microglial cells and the knockdown of TRIM8 protected microglial cells from OGD -induced cytotoxicity and inflammation. Moreover, TRIM8 knockdown or miR-665-3p overexpression blocked OGD-induced activation of nuclear factor (NF)-κB signaling in microglial cells. In addition, TRIM8 overexpression partially reversed the miR-665-3p overexpression-mediated inhibitory effect on OGD-induced inflammation in microglial cells. Taken together, these results indicate that miR-665-3p up-regulation protects microglial cells from OGD-induced apoptosis and inflammatory response by targeting TRIM8 to inhibit NF-κB signaling. [ABSTRACT FROM AUTHOR]

• TRIM8 expression is increased in OGD/R-exposed neurons. • TRIM8 inhibition protects from OGD/R-induced neuronal injury. • TRIM8 inhibition enhances Nrf2 signaling by regulating AMPK. • TRIM8 regulates OGD/R-induced neuronal injury by AMPK/Nrf2 signaling. Tripartite motif 8 (TRIM8) has emerged as a crucial regulator of cell survival, apoptosis, and oxidative stress in various pathological processes. However, TRIM8's involvement in regulating neuronal injury in cerebral ischemia/reperfusion injury remains largely uncharacterized. In the present study, we aimed to investigate the potential function and molecular mechanism of TRIM8 in regulating neuronal apoptosis and oxidative stress induced by oxygen–glucose deprivation/re-oxygenation (OGD/R) in an in vitro model to study cerebral ischemia/reperfusion injury. Herein, we found that TRIM8 expression was upregulated in neurons exposed to OGD/R. Knockdown of TRIM8 improved the viability and decreased the apoptosis and reactive oxygen species (ROS) generation in OGD/R-exposed neurons, whereas TRIM8 overexpression showed the opposite effect. Notably, TRIM8 inhibition increased the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and enhanced the nuclear expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2). Moreover, TRIM8 inhibition promoted the transcriptional activity of the Nrf2/antioxidant response element (ARE). However, AMPK inhibition partially reversed TRIM8 downregulation-mediated Nrf2/ARE activation and the neuroprotective effect in OGD/R-exposed neurons. Additionally, silencing of Nrf2 also markedly abrogated TRIM8 downregulation-mediated neuroprotection. Overall, these results demonstrate that downregulation of TRIM8 protects from OGD/R-induced neuronal injury by reinforcing the activation of Nrf2/ARE antioxidant signaling via AMPK, suggesting a potential role for TRIM8 in cerebral ischemia/reperfusion injury. [ABSTRACT FROM AUTHOR]

Background: Sepsis-associated encephalopathy (SAE) is prevalent in intensive care unit (ICU) environments but lacks established treatment protocols, necessitating prompt diagnostic methods for early intervention. Traditional symptom-based diagnostics are non-specific and confounded by sedatives, while emerging biomarkers like neuron-specific enolase (NSE) and S100 calcium-binding protein B (S100B) have limited specificity. Transcranial Doppler (TCD) indicators, although is particularly relevant for SAE, requires high operator expertise, limiting its clinical utility., Objective: This pilot study aims to utilize cerebral circulation time (CCT) assessed via contrast-enhanced ultrasound (CEUS) as an innovative approach to investigate the accuracy of SAE prediction. Further, these CCT measurements are integrated into a nomogram to optimize the predictive performance., Methods: This study employed a prospective, observational design, enrolling 67 ICU patients diagnosed with sepsis within the initial 24 h. Receiver operating characteristic (ROC) curve analyses were conducted to assess the predictive accuracy of potential markers including NSE, S100B, TCD parameters, and CCT for SAE. A nomogram was constructed via multivariate Logistic Regression to further explore the combined predictive potential of these variables. The model's predictive performance was evaluated through discrimination, calibration, and decision curve analysis (DCA)., Results: SAE manifested at a median of 2 days post-admission in 32 of 67 patients (47.8%), with the remaining 35 sepsis patients constituting the non-SAE group. ROC curves revealed substantial predictive utility for CCT, pulsatility index (PI), and S100B, with CCT emerging as the most efficacious predictor, evidenced by an area under the curve (AUC) of 0.846. Multivariate Logistic Regression identified these markers as independent predictors for SAE, leading to the construction of a nomogram with excellent discrimination, substantiated by an AUC of 0.924 through bootstrap resampling. The model exhibited satisfactory concordance between observed and predicted probabilities, and DCA confirmed its clinical utility for the prompt identification of SAE., Conclusion: This study highlighted the enhanced predictive value of CCT in SAE detection within ICU settings. A novel nomogram incorporating CCT, PI, and S100B demonstrated robust discrimination, calibration, and clinical utility, solidifying it as a valuable tool for early SAE intervention., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Mei, Zhang, Sun, Hu and Song.)

Objective To investigate the alterations in hippocampus neuron morphology, the expression of neurogenin 2 (Ngn2) and methyl-CpG-binding protein 2 (MeCP2) in hippocampus after electromagnetic pulse (EMP) irradiation. Methods Adult healthy male SD rats were randomly divided into control group, EMP 7-day group, and EMP 14-day group (n=12). Hippocampus neuron morphology was tested by HE staining; the expression of Ngn2 and MeCP2 were measured by Western blotting and fluorescent immunohistochemistry; the protein levels of brain-derived neurotrophic factor (BDNF) and postsynaptic density protein 95 (PSD95) were measured by Western blotting. Results Compared with the control group, the number of pyramidal cells in the EMP 7-day group and EMP 14-day group was reduced, the neuron boundary was blurred, and the nuclear outline was blurred. Compared with the EMP 7-day group, the hippocampus neuron structure in the EMP 14-day group was more severely damaged. Compared with the control group, the expression of Ngn2, BDNF, and PSD95 significantly decreased, while the expression of MeCP2 increased in the EMP 14-day group and EMP 7-day group. Conclusion EMP exposure leads to the pathological damage of hippocampus neurons in rats, increases MeCP2 expression and decreases Ngn2, PSD95, BDNF expression.

Background: Endogenous cannabinoid anandamide (AEA) protects neurons from oxidative injury in rodent models; however the mechanism of AEA-induced neuroprotection remains to be determined. Activation of neuronal NADPH oxidase 2 (Nox2) contributes to oxidative damage of the brain, and inhibition of Nox2 can attenuate cerebral oxidative stress. We aimed to determine whether the neuronal Nox2 was involved in protection mediated by AEA., Methods: The mouse hippocampal neuron cell line HT22 was exposed to hydrogen peroxide (H2O2) to mimic oxidative injury of neurons. The protective effect of AEA was assessed by measuring cell metabolic activity, apoptosis, lactate dehydrogenase (LDH) release, cellular morphology, intracellular reactive oxygen species (ROS), and antioxidant and oxidant levels and Nox2 expression., Results: HT22 cells exposed to H2O2 demonstrated morphological changes, decreased LDH release, reduced metabolic activity, increased levels of intracellular ROS and oxidized glutathione (GSSG), reduced levels of superoxide dismutase (SOD), and reduced glutathione (GSH) and increased expression of Nox2. AEA prevented these effects, a property abolished by simultaneous administration of CB1 antagonist AM251 or CB1-siRNA., Conclusion: Nox2 inhibition is involved in AEA-induced cytoprotection against oxidative stress through CB1 activation in HT22 cells.