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.

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.