Apamin, an SK2 Inhibitor, Attenuated Neonatal Sevoflurane Exposures Caused Cognitive Deficits in Mice through the Regulation of Hippocampal Neuroinflammation.

Cognitive dysfunction induced by anesthesia in the infant is a crucial clinical issue that is still being debated and the focus of concern for the parents. However, the mechanism of cognitive decline caused by anesthesia and the corresponding treatment methods remain unclear. Postnatal day 7 (PND7) C57BL/6 mice included in the study were randomly divided into a control group (Control), a group with repeated exposure to sevoflurane (Sevo), and an Apamin intervention group (Sevo + Apamin). Apamin (0.5 µL at the concentration of 100 nmol/L) was injected into the bilateral hippocampus of mice. qRT-PCR, enzyme-linked immunosorbent assay (ELISA), and western blotting assay were used to evaluate the protein levels in the hippocampus. Object location memory (OLM) and novel object recognition (NOR) tasks, as well as elevated plus maze and contextual and cued fear conditioning tasks were used to evaluate the cognitive function of mice. Apamin mitigated sevoflurane-induced cognitive impairment of mice, sevoflurane-induced neuronal injury, and sevoflurane-induced activation of microglial in the hippocampus of the mice. Apamin inhibited M1-type polarization but promoted M2-type polarization of microglia after neonatal sevoflurane exposures in the hippocampus. In conclusion, Apamin attenuates neonatal sevoflurane exposures that cause cognitive deficits in mice through regulating hippocampal neuroinflammation.

Modified Long-Axis In-plane Technique for Radial Artery Cannulation in Children: A Randomized Controlled Trial.

BACKGROUND: Radial artery catheterization is a challenge for anesthetists in the pediatric population. The purpose of this study was to determine whether the modified long-axis in-plane (MLAX-IP) technique increased the success rate of radial artery catheterization in children. METHODS: This study involved 80 children who required arterial catheterization and were randomly divided into the MLAX-IP group and dynamic needle tip positioning (DNTP) group (40 cases in each group). Radial artery catheterization was performed using either the MLAX-IP technique or the DNTP technique. RESULTS: The first-attempt cannulation success rate was higher in the MLAX-IP group than in the DNTP group (95 vs. 80%, P = 0.043). The imaging time of the artery in the MLAX-IP group was longer than in the DNTP group (19.1 ± 3.1 vs. 9.6 ± 2.4 s, P < 0.001). While the total catheterization time was similar between the 2 groups (88.1 ± 23 vs. 86.9 ± 46.1 s, P = 0.475). CONCLUSION: The first-attempt cannulation success rate with the MLAX-IP technique is increased, while the total catheterization time is similar between the 2 groups and puncture-related complications are fewer.

Effects of Adding Oxycodone to Ropivacaine on Labor Analgesia: A Randomized Controlled Trial.

BACKGROUND: It has been reported that oxycodone is superior to the other opioids for the treatment of visceral pain. During the first stage of labor, pain is mainly caused by uterine contractions (visceral pain). It seems that oxycodone is more suitable for labor analgesia. During this study, we investigated the effects of adding oxycodone to ropivacaine on epidural analgesia during labor. MATERIALS AND METHODS: Eighty nulliparous parturients were randomly divided into 2 groups. Group A received 0.2 mg/mL oxycodone plus 0.1% ropivacaine for epidural analgesia and group C (control group) received 0.1% ropivacaine alone for epidural analgesia. The onset time and duration of analgesia, duration of labor stages, delivery outcome, analgesic effect, Bromage scores, blood pressure, heart rate, and neonatal Apgar scores were recorded. Umbilical arterial blood was collected to analyze. Side effects, if any, were also recorded. RESULTS: The visual analog scale of pain was lower at 2 and 4 hours after analgesia and 10 cm cervical dilatation in group A compared with group C (P=0.021, 0.018, and 0.009, respectively). The onset time of analgesia was shorter in group A than that in group C (13.3±2.8 vs. 14.9±3.6 min, P=0.032). There were no significant differences between the 2 groups in terms of the duration of labor stages, delivery outcome, Bromage score, neonatal Apgar score, or umbilical arterial blood pH. The duration of analgesia was significantly longer in group A than in group C (326.2±56.5 vs. 68.4±10.5 min, P=0.000), but the incidence of pruritus was higher in group A than in group C (10% vs. 0%, P=0.115). CONCLUSIONS: This study demonstrates that epidural oxycodone may accelerate the onset of analgesia and obviously prolong the duration of analgesia during labor without increasing adverse effects associated with the neonate. However, it may cause a higher incidence of maternal pruritus (registration number: ChiCTR1800016483).

The neuroprotective mechanism of 2-arachidonoylglycerol 2-AG against non-caspase-dependent apoptosis in mice hippocampal neurons following MCAO.

OBJECTIVE: In this study, the neuroprotective mechanism of 2-arachidonoylglycerol 2-AG against non-caspase-dependent apoptosis in mice hippocampal neurons following MCAO was investigated. METHOD: One hundred and fifty healthy clean male C57BL/6 mice were randomly divided into 3 groups: sham group, model group and 2-AG treatment group, 50 mice in each group. A modified Zea Longa method was used to establish a model of middle cerebral artery occlusion (MCAO) in mice. The apoptosis rate and mitochondrial membrane potential of hippocampal nerve cells were measured by flow cytometry. The mRNA expressions of AIF, Endo G and BNIP3 in hippocampal tissues were determined by qPCR. Western blot was used to determine the protein expressions of AIF, Endo G and BNIP3 in the mitochondria of hippocampal tissue. RESULTS: The apoptosis rate of hippocampal neurons in the group treated with 2-AG was significantly lower than that of the model (P<0.01), which indicated that 2-AG could inhibit the apoptosis of hippocampal neurons induced by MCAO. However, the mitochondrial membrane potential of hippocampal neurons in the group treated with 2-AG was significantly higher than that of the model (P<0.01), indicating that 2-AG could improve the mitochondrial membrane potential of hippocampal neurons in MCAO mice. Real-time quantitative PCR (qPCR) showed that 2-AG could inhibit the gene expressions of AIF, Endo G and BNIP3 in hippocampal tissues. Western blot results showed that 2-AG could inhibit the secretions of AIF, Endo G and BNIP3 into cytoplasm in mitochondria. CONCLUSION: Endocannabinoids 2-AG had a protective effect on neurons injury, and the mechanism was possibly associated with the protection of the brain nerve cells in the hippocampus and the integrity of the mitochondrial function. Endocannabinoids 2-AG may inhibit the non-caspase-dependent apoptosis pathway, so as to exert its nerve protective effect.

The role of the GABA-A receptor of the adjacent intact dorsal root ganglion neurons in rats with neuropathic pain.

We aim to investigate the changes of The γ-aminobutyric acid (GABA) signals in the adjacent intact dorsal root ganglion (DRG) and the contribution of these changes to the development and maintenance of neuropathic pain (NPP). After establishment of neuropathic pain model with the lumbar 5 spinal nerve ligation (L5 SNL), the GABA-evoked currents were recorded in the acutely dissociated L4 DRG neurons using whole-cell patch clamp. Moreover, Muscimol or Bicuculline were respectively topically injected to the L4 DRG at the time of nerve injury and post-operative 5 days (POD5). The pain thresholds of hind paw were recorded. We found that the incidence and amplitude of GABA currents significantly decreased in the large and medium L4 DRG neurons after SNL (P<0.05). Furthermore, in the L5 SNL rats, 20 µg Muscimol injected immediately after injury caused a long-lasting attenuation of mechanical allodynia (P<0.05), whereas the thermal hyperalgesia was not alleviated (P>0.05). 0.15 µg Bicuculline further decreased the pain thresholds (P<0.05) and reversed the pain-alleviating effects of Muscimol. However, at POD5, 20 µg Muscimol only exhibited transient alleviating effects (P<0.05). In conclusion, the decrease of inhibition signal mediated by GABA-A receptor in the adjacent intact DRG neurons may be crucial in the development of hyperalgesia in NPP.

Neuroprotective effect of calcitriol on ischemic/reperfusion injury through the NR3A/CREB pathways in the rat hippocampus.

Calcitriol has been demonstrated to provide neuroprotection against ischemia/reperfusion (I/R) injury. However, the exact mechanism of this protection remains unknown. In the present study, the neuroprotective effect of calcitriol was investigated in rats exposed to cerebral I/R injury induced by middle cerebral artery occlusion (MCAO). In addition, the involvement of NR3A, extracellular signal­regulated kinase 1/2 (ERK1/2), and phosphorylated cAMP/Ca2+­response element binding protein (p­CREB) in this protective action was determined in the hippocampal neurons. Western blot analysis was conducted to analyze the protein levels of NR3A, mitogen­activated protein kinase kinase (MEK) and p­CREB. The immunoreactivity of p­CREB and NR3A were measured by quantum dot­based immunofluorescence analysis. Results showed that MCAO rats exhibited large cortical infarct volumes. By contrast, intraperitoneal administration of calcitriol significantly reduced infarct volumes seven days following reperfusion, and these results were accompanied by elevated NR3A and p­CREB activity in the hippocampal neurons. The inhibition of MEK by the addition of PD98059 led to attenuation of the neuroprotective effects of calcitriol and a correlated decrease in CREB activity. The results also demonstrated that calcitriol protected the brain from I/R injury through the NR3A­MEK/ERK­CREB pathway.