Icariin mitigates anxiety-like behaviors induced by hemorrhagic shock and resuscitation via inhibiting of astrocytic activation.

BACKGROUND: Abnormal activation of astrocytes in the amygdala contributes to anxiety after hemorrhagic shock and resuscitation (HSR). Nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB)-associated epigenetic reprogramming of astrocytic activation is crucial to anxiety. A bioactive monomer derived from Epimedium icariin (ICA) has been reported to modulate NF-κB signaling and astrocytic activation. PURPOSE: The present study aimed to investigate the effects of ICA on post-HSR anxiety disorders and its potential mechanism of action. METHODS: We first induced HSR in mice through a bleeding and re-transfusion model and selectively inhibited and activated astrocytes in the amygdala using chemogenetics. Then, ICA (40 mg/kg) was administered by oral gavage once daily for 21 days. Behavioral, electrophysiological, and pathological changes were assessed after HSR using the light-dark transition test, elevated plus maze, recording of local field potential (LFP), and immunofluorescence assays. RESULTS: Exposure to HSR reduced the duration of the light chamber and attenuated open-arm entries. Moreover, HSR exposure increased the theta oscillation power in the amygdala and upregulated NF-κB p65, H3K27ac, and H3K4me3 expression. Contrarily, chemogenetic inhibition of astrocytes significantly reversed these changes. Chemogenetic inhibition in astrocytes was simulated by ICA, but chemogenetic activation of astrocytes blocked the neuroprotective effects of ICA. CONCLUSION: ICA mitigated anxiety-like behaviors induced by HSR in mice via inhibiting astrocytic activation, which is possibly associated with NF-κB-induced epigenetic reprogramming.

The Effect of the Magnesium Sulfate in Ultrasound-Guided Quadratus Lumborum Block on Postoperative Analgesia: A Randomized Controlled Trial.

INTRODUCTION: Quadratus lumborum block (QLB) has proven to be an effective analgesic technique in various abdominal surgeries. Magnesium sulfate as an adjuvant in different nerve blocks has been reported. The aim of this study was to assess the efficacy of magnesium sulfate as an adjuvant to ropivacaine in an ultrasound-guided QLB for postoperative analgesia in laparoscopic gynecologic surgery. METHODS: Ninety patients belonging to American Society of Anesthesiologists (ASA) physical status I or II, aged between 40 and 60 years, scheduled for laparoscopic gynecologic surgery were enrolled. Patients were divided into three groups and received bilateral quadratus lumborum block: ropivacaine group (group N, 0.375% ropivacaine 40 ml + normal saline 4 ml), magnesium sulfate group (group M, 0.375% ropivacaine 40 ml + 10% magnesium sulfate 4 ml), and control group (group C, normal saline 44 ml). Visual analogue scale (VAS) at rest and during activity at 4, 6, 12, 24, and 48 h postoperatively, consumption of morphine, the time of first analgesic request, frequency of rescue analgesia, satisfaction with postoperative analgesia, and any side effects were recorded. RESULTS: VAS scores in groups M and N were significantly lower than in group C at 4 and 6 h postoperatively (P < 0.001). VAS scores were lower in group M at 12 and 24 h postoperatively compared to groups N and C (P < 0.05). The mean total morphine consumption was significantly lower in group M than in groups N and C (P < 0.001). The mean time to the first patient-controlled analgesia (PCA) bolus was significantly prolonged in group M compared to group C (P < 0.05). The satisfaction with postoperative analgesia of group M was superior to that of groups N and C (P < 0.05). There was no significant difference in side effects among the three groups. CONCLUSION: Magnesium sulfate as an adjuvant to ropivacaine in ultrasound-guided QLB prolongs the duration of analgesia, decreases analgesic requirements, and improves patient satisfaction without significant side effects. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900027066.

Selenium Deficiency Induces Inflammatory Response and Decreased Antimicrobial Peptide Expression in Chicken Jejunum Through Oxidative Stress.

Selenium deficiency can affect the level of selenoprotein in organs and tissues and cause inflammation. However, the mechanism of selenium deficiency on jejunal injury in chickens remains unclear. In this study, we established a selenium deficiency model in chickens by feeding a low selenium diet and observed ultrastructural and pathological changes in the jejunum. The expression levels of 25 selenoproteins, the levels of oxidative stress, tight junction (TJ) proteins, and antimicrobial peptides (AMP), as well as the expression levels of factors related to inflammatory signaling pathways, were examined in the intestine and analyzed using principal component analysis (PCA). The results of PCA and quantitative real-time PCR (qRT-PCR) showed that selenium deficiency mainly affected the expression of antioxidant selenoproteins in chicken jejunum, especially glutathione peroxidases, thioredoxin reductase, and iodothyronine deiodinase, thus weakening the antioxidant function in the intestine and inducing oxidative stress. We also found disruption of intestinal TJ structures, a significant reduction in TJ protein expression, and downregulation of antimicrobial peptide levels, suggesting that selenium deficiency led to damage of the intestinal barrier. In addition, a significant increase in inflammatory cell infiltration and expression of inflammatory factors was observed in the jejunum, indicating that selenium deficiency induces inflammatory injury. In conclusion, selenium deficiency downregulates antioxidant selenoproteins levels, induces oxidative stress, decreases intestinal AMP levels, and leads to inflammatory injury and disruption of the intestinal barrier in the jejunum. These results shed new light on the molecular mechanisms of intestinal damage caused by selenium deficiency.

MiR-129-3p regulates ferroptosis in the liver of Selenium-deficient broilers by targeting SLC7A11.

Selenium (Se) has been proven to be an essential trace element for organism. Se deficiency in poultry can cause widespread damage, such as exudative diathesis. The liver is not only the main organ of metabolism, but also one of the organs with high Se content in organism. Recent studies have shown that solute carrier family 7 member 11 (SLC7A11) plays a key role in the negative regulation of ferroptosis. In order to explore the mechanism of Se deficiency induces liver ferroptosis in broilers, and the role of microRNAs (miRNAs) in this process, we divided broilers into 2 groups: control group (0.2 mg/kg Se) and Se deficiency group (0.03 mg/kg Se). Hematoxylin-Eosin staining detected liver tissue damage in broilers. Predicted and verified the targeting relationship between miR-129-3p and SLC7A11 through miRDB and dual luciferase report experiments. The genes related to ferroptosis were detected by qRT-PCR and Western Blot. The results showed that the expression level of miR-129-3p mRNA in Se-deficient liver was significantly increased. To understand whether the miR-129-3p/SLC7A11 axis could involve in the process of ferroptosis, our further research showed that overexpression of miR-129-3p could reduce the expression of SLC7A11 and its downstream GCL, GSS, and GPX4, thereby inducing ferroptosis. These data indicates that miR-129-3p affected ferroptosis under Se deficiency conditions through the SLC7A11 pathway. Our research provides a new perspective for the mechanism of Se deficiency on the liver damage.

Thalamus Cavernous Malformation Resection of via Contralateral Anterior Interhemispheric Transcallosal Approach: Two-Dimensional Operative Video.

Thalamic cavernous malformations (CM) are highly challenging surgically. In this illustrative video (Video 1), we present the case of a 36-year-old man with a CM at the left medial thalamus, which was successfully treated by a contralateral anterior interhemispheric transcallosal approach. Informed consent was obtained from the patient. Preoperative imaging demonstrated that the CM appeared to have reached the pial surface superiorly and medially, and diffusion tensor imaging showed the pyramidal tracts to be traveling laterally to the CM. Based on the "Two-point" principle and to avoid pyramidal tract impingement, an anterior interhemispheric transcallosal approach was chosen. Furthermore, to avoid excessive retraction on the ipsilateral hemisphere, we selected the contralateral trajectory over the ipsilateral trajectory. The head was positioned with the right side down; thus, the space between the right hemisphere and the falx could expand because of gravity autoretraction, which could minimize the need of retraction during the interhemispheric dissection. A small incision on the corpus callosum was performed under the guidance of neuronavigation, and the left ventricle was subsequently entered. After a thin layer of hemosiderin-stained pia was opened on the superior surface of the left thalamus, some sandlike old hemorrhagic component was removed for decompression, and the lesion was carefully dissected away from the normal parenchyma within the surrounding gliosis boundary. The CM was removed en bloc, and the deep venous anomaly was well protected. The patient did not experience any intraoperative changes shown by electrophysiologic monitoring, and he recovered well postoperatively.

Sevoflurane pre-conditioning increases phosphorylation of Erk1/2 and HO-1 expression via inhibition of mPTP in primary rat cortical neurons exposed to OGD/R.

BACKGROUND: As an indispensable clinical inhalation anesthetic, sevoflurane is widely used for peri-operative sedation. The neuroprotective effect of sevoflurane pre-conditioning against cerebral ischemia/reperfusion has been gradually realized, but the underlying mechanism during the early reperfusion period has not been established. METHOD: Primary cultured cortical neurons were treated with 2% sevoflurane pre-conditioning for 30min, exposed to oxygen-glucose deprivation for 90min, and followed by 60min of reperfusion (OGD/R). Additionally, neuronal cells were treated with an inhibitor of extracellular signal-related kinases 1 and 2 (Erk1/2) phosphorylation (PD98059), a mPTP opener (atractyloside), or a mPTP opening inhibitor (cyclosporine A) before sevoflurane pre-conditioning. RESULT: Sevoflurane pre-conditioning decreased neuronal apoptosis (assessed by TUNEL), oxidative stress (assessed by malondialdehyde [MDA], superoxide dismutase [SOD], and heme oxygenase [HO]-1), and opening of mitochondrial permeability transition pores [mPTPs] (assessed by calcein-cobalt), but increased neuronal viability (assessed by MTT) and mitochondrial membrane potential (assessed by JC-1) after OGD/R exposure compared with OGD/R treatment alone. Pre-treatment with the mPTP opener and inhibitor of Erk1/2 phosphorylation abolished the protective effect induced by sevoflurane pre-conditioning. Pre-treatment with the mPTP opener attenuated the phosphorylation of Erk1/2 in mitochondria of neuronal cultures exposed to OGD/R induced by sevoflurane pre-conditioning. The mPTP opening inhibitor, like sevoflurane pre-conditioning, increased phosphorylation of Erk1/2 after OGD/R exposure, while PD98059 failed to reverse inhibition of mPTP opening in cultures exposed to OGD/R induced by sevoflurane pre-conditioning. CONCLUSION: The neuroprotective mechanism of sevoflurane pre-conditioning might be associated with increased Erk1/2 phosphorylation in mitochondria via inhibition of mPTP opening in the early reperfusion period.

PGE2 receptor agonist misoprostol protects brain against intracerebral hemorrhage in mice.

Intracerebral hemorrhage (ICH) is a devastating form of stroke. Misoprostol, a synthetic prostaglandin E1 (PGE1) analog and PGE2 receptor agonist, has shown protection against cerebral ischemia. In this study, we tested the efficacy of misoprostol in the 12-month-old mice subjected to 1 of 2 complementary ICH models, the collagenase model (primary study) and blood model (secondary study, performed in an independent laboratory). We also investigated its potential mechanism of action. Misoprostol posttreatment decreased brain lesion volume, edema, and brain atrophy and improved long-term functional outcomes. In the collagenase-induced ICH model, misoprostol decreased cellular inflammatory response; attenuated oxidative brain damage and gelatinolytic activity; and decreased high-mobility group box 1 (HMGB1) expression, Src kinase activity, and interleukin-1ß expression without affecting cyclooxygenase-2 expression. Furthermore, HMGB1 inhibition with glycyrrhizin decreased Src kinase activity, gelatinolytic activity, neuronal death, and brain lesion volume. Src kinase inhibition with 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP2) decreased gelatinolytic activity and brain edema and improved neurologic function but did not decrease HMGB1 protein level. These results indicate that misoprostol protects brain against ICH injury through mechanisms that may involve the HMGB1, Src kinase, and matrix metalloproteinase-2/9 pathways.