Effect of NMDAR-NMNAT1/2 pathway on neuronal cell damage and cognitive impairment of sevoflurane-induced aged rats.

Objective: The possible effect of NMDAR (N-methyl-D-aspartate receptor)-NMNAT1/2 (nicotinamide/nicotinic acid mono-nucleotide adenylyltransferase) signaling pathway on the neuronal cell damage and cognitive impairment of aged rats anesthetized by sevoflurane was explored.Methods: Adult male Wistar rats were selected and divided into Control, Sevo (Sevoflurane), Sevo+DCS (NMDAR agonist D-cycloserine) 30 mg/kg, Sevo+DCS 100 mg/kg, and Sevo+DCS 200 mg/kg groups. Morris water maze and fear conditioning text were used to observe cognitive function changes of rats. The inflammatory cytokines were determined by quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) assay, neuronal apoptosis by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labelling (TUNEL) staining and MDAR-NMNAT1/2 pathway-related proteins by Western blotting.Results: The longer escape latency, decreased platform crossing times and reduced staying time spent in platform quadrant were found in rats from Sevo group, with decreased percentage of freezing time in contextual test and tone cued test; and meanwhile, these rats had increased inflammatory cytokines (interleukin (IL)-1ß, tumor necrosis factor (TNF-α), IL-6, and IL-8) and neuronal apoptosis, but declined expressions of MDAR-NMNAT1/2 pathway-related proteins. However, the above changes were exhibited an opposite tendency in those Sevo rats treated with different concentrations of DCS (including 30, 100, and 200 mg/kg, respectively). Particularly, the improving effect of low-dose DCS on each aspect in aged rats was better than high-dose ones.Conclusion: Activation of NMDAR-NMNAT1/2 signaling pathway could not only reduce neuronal apoptosis, but also alleviate sevoflurane-induced neuronal inflammation and cognitive impairment in aged rats.

IL-17A promotes the neuroinflammation and cognitive function in sevoflurane anesthetized aged rats via activation of NF-κB signaling pathway.

BACKGROUND: To investigate the role of IL-17A in the neuroinflammation and cognitive function of aged rats anaesthetized with sevoflurane through NF-κB pathway. METHOD: The aged and young adult rats were randomly divided into Control (inhale oxygen only), Sevoflurane (inhale oxygen and sevoflurane), Sevo (Sevoflurane) + anti-IL-17A (injected with IL-17A antibody, inhale oxygen and sevoflurane), and Sevo + NC groups (injected with IgG2a antibody, inhale oxygen and sevoflurane). Cognitive function was evaluated by Morris water maze and contextual fear conditioning tests. Tumor necrosis factor (TNF)-α, Interleukin (IL)-1ß, IL-6 and monocyte chemoattractant protein (MCP)-1 expressions in the hippocampus of rats were detected by ELISA (enzyme-linked immunosorbent assay) assay, and Nuclear factor (NF)-κB pathway-related proteins by Western blot. RESULTS: Sevoflurane anaesthetized aged rats showed longer escape latency and swimming distance, fewer platform crossing times, shortened stay time in the platform quadrant compared to Control rats; In addition, increased levels in hippocampal expression of malondialdehyde (MDA), IL-17A, NF-κB p65, inducible nitric oxide synthase (iNOS) and COX-2, as well as a reduced level of superoxide dismutase (SOD) were also observed in these animals. However, the sevoflurane anesthetized aged rats treated with anti-IL-17A presented a completely opposite tendency concerning the above factors (all P < 0.05). Nevertheless, there was no significant difference in the acquisition of learning or memory, neuroinflammation and oxidative stress of young adult rats in all groups (all P > 0.05). CONCLUSION: Anti-IL-17A may alleviate neuroinflammation and oxidative stress via inhibiting NF-κB pathway, thereby attenuating post-operative cognitive dysfunction (POCD) in aged rats anaesthetized with sevoflurane.

Effect of Wnt signaling pathway on pathogenesis and intervention of neuropathic pain.

Neuropathic pain (NP) is a common clinical chronic pain with very complex mechanisms. This study explored the function of activated Wnt signaling pathway in NP. A rat model of chronic constriction injury (CCI) was established. Different doses of IWP-2, a Wnt signal inhibitor, were intrathecally injected to observe the behavior indicators at different time-points, including the pain induced by mechanical stimulation and thermal stimulation. The mRNA and protein levels of Wnt-3a, Frizzled 4 and ß-catenin in lumbar (L) 4-6 dorsal root ganglion (DRG) of rats in each group, as well as synaptic plasticity-related molecules in DRG region of rats were detected by RT-PCR and western blotting, respectively. Compared with Sham group and Naive group, paw withdrawal thermal latency and paw withdrawal mechanical threshold were significantly decreased after CCI, while synaptic plasticity was increased (P<0.05). Besides, activation of Wnt/ß-catenin signaling pathway was observed in rats with CCI. We found that intrathecal injection of IWP-2 effectively relieved the pain behavior and reduced the synaptic plasticity in rats with neuropathic pain after CCI, suggesting that the inactivated Wnt/ß-catenin signaling pathway might be the major mechanism responsible for this effect. Our data demonstrated that intrathecal injection of IWP-2 ameliorated neuropathic pain in CCI rats by inhibiting the Wnt/ß-catenin pathway.

The changes of pulmonary blood flow in non-ventilated lung during one lung ventilation.

OBJECTIVE: A pulmonary artery catheter placement is necessary for intrapulmonary shunt fraction evaluation. The purpose of this study was to investigate the feasibility for detecting the changes of regional pulmonary blood flow in non-ventilated lung by transesophageal echocardiography (TEE) during one-lung ventilation (OLV). METHODS: 22 adult patients for selective thoracic surgery were enrolled in the study. Doppler flow patterns in left upper pulmonary vein (LUPV) were obtained by TEE before switching to right OLV and every 5 min in 30 min OLV period. Systolic peak velocity (Vs), diastolic peak velocity (Vd) and velocity time integral (VTI) were measured respectively. RESULTS: The VTI of LUPV blood flow pattern decreased significantly 5 min after right OLV. The percent of changes in LUPV blood flow decreased rapidly by 78.4 and 67.7% at OLV 5 min and 10 min, respectively. Then it slowly decreased by 60% at OLV 30 min. CONCLUSIONS: Provides an alternative method to measure the changes of pulmonary blood flow during OLV. The percent changes of regional pulmonary blood flow decreased immediately after OLV, and decreased by 60% at 30 min OLV.

[The pulmonary arterial oxygen saturation monitoring via trachea in hypoxia dogs].

This study was aimed to assess the agreement between pulse pulmonary arterial oxygen saturation (StO2) by oximetry in trachea and the mixed venous oxygen saturation (SvO2) by fiberoptic pulmonary arterial catheter, and to evaluate the accuracy of StO2 monitoring during hypoxia. 10 mongred dog's were used. After anesthesia was induced and thorax was opened, we placed a fiberoptic pulmonary artery catheter directly through the dog's right ventricular outlet. Then, we placed and adjusted the trachea catheter, attached the oximetry probe to trachea carina till the high quality StO2 PPG signal was obtained, and till the readings were stable at about +/-2% from fiberoptic catheter. The pair readings of StO2 and SvO2 were recorded at every minute interval in 10 minutes when circulation was stable. Decreasing the inhaled oxygen concentration till the tongue's SpO2 decreased to 60%; recording the changes of StO2 and SvO2 in every 5% drop of tongue's SpO2 when the tongue's SpO2 decreased from 100% to 50%. The results showed that there was a good agreement between the two methods for pulmonary arterial oxygen saturation measurement. However, the difference between the two methods was great and unacceptable during the presence of hypoxia.