Attractylone attenuates sepsis-associated encephalopathy and cognitive dysfunction by inhibiting microglial activation and neuroinflammation.

Multiple studies demonstrated that sepsis is a life-threatening state of organ dysfunction caused by infection and can induce neuroinflammation and cognitive impairment. The aim of this study was to evaluate the protective effects of attractylone (Atr) on sepsis-associated encephalopathy (SAE) and cognitive dysfunction. Moreover, we studied the underlying molecular mechanisms. We used an LPS-induced sepsis mouse model and evaluated the cognitive function with the Morris water maze and open field test. Neuronal damage in the hippocampus was assessed by immunohistochemical analysis. BV2 cells were used to identify the protective mechanism of Atr. The result showed that Atr attenuated LPS-induced cognitive impairment, neural apoptosis, inflammatory factors, and microglial activation. The in vitro experiment showed that Atr promoted silent information regulator 1 (SIRT1) expression and suppressed NFκB expression. Downregulation of SIRT1 reversed the protective effect of Atr in the LPS condition. Moreover, Atr-induced SIRT1 expression promoted BV2 from LPS-induced M1 to M2 phenotype. Taken together, these results indicated that Atr was a potential therapeutic agent for SAE and cognitive dysfunction.

Distinct Hippocampal Expression Profiles of lncRNAs in Rats Exhibiting a PTSD-like Syndrome.

Posttraumatic stress disorder (PTSD) refers to a series of clinical syndromes, including symptoms such as nightmares, hallucinations, severe anxiety, fear, and trauma related to the environment. These symptoms tend to occur after intense psychological trauma or physiological stress. Long non-coding RNAs (lncRNAs) have been shown to play key roles in various biological processes, although it is unknown whether they have important functions in PTSD. Here, we present the first study exploring the connection between lncRNAs and a PTSD-like syndrome in rats. We find distinct expression profiles of lncRNAs between PTSD-like syndrome rats and a control group, which provides information for further research on the differentiation of PTSD and transdifferentiation between the PTSD-like syndrome and the control group. This information will be helpful for finding new therapeutic targets for the treatment of PTSD.

Effects of intrathecal injection of acetyltransferase p300 inhibitor Garcinol on neuropathic pain in rat model of L5 spinal nerve ligation / 临床麻醉学杂志

Objective To explore the effects of intrathecal injection of acetyltransferase p300 inhibitor Garcinolon on hyperalgesia in a rat model of L5 spinal nerve ligation and its underlying mechanism. Methods After lumber intrathecal catheters implanted,90 male Sprague-Dawley rats (40-50 d,weighing 180-220 g)were randomly divided into six groups (n=15 each):Naive group (group N),Sham operation group (group S),SNL group (group C)and three Garcinol treatment groups (group H:500μg/kg,group M:100μg/kg,group L:20μg/kg).Group N did not receive any operation in rats.In group S,the L5 spinal nerve was only exposed without ligation.Other four groups all received spinal nerve ligation (SNL).Group N,group S and group SNL were administrated intrathcelly with 100% DMSO (10 μl)within 3 to 6 days after SNL surgery.Other three groups were treated with Garcinol 500μg/kg (group H),100μg/kg (group M),20 μg/kg (group L)at the same points respectively.Behaviorally,thermal withdrawal latency (TWL) were measured at 1 day (T0 )before and on days 1(T1 ),3(T2 ),5(T3 ),7(T4 ),9(T5 ),11(T6 ),14(T7 )after surgery separately.On the 7th day after behavioral testing,the lumber segment of the spinal cord was removed to test the level of p300 and acetyl-p65 by western blot,while NF-κB was detected with immunofluorescence. Results Compared with group N,TWL was significantly shortened in group C,L,M and H,the levels of ace-tyl-p65 and p300 in group C,L,M and H were markedly increased,the expression of NF-κB in group C,L,M and H was markedly increased(P<0.05).Compared with group C,TWL was significantly prolonged in group M and group H,the levels of acetyl-p65 and p300 in group M and group H were dramatically decreased,the expression of NF-κB in group H was obviously decreased(P <0.05).Conclusion The acetyltransferase p300 inhibitor Garcinol imposes protective effect in SNL-induced neuropathic pain.Mechanisms are probably associ-ated with decreasing acetyl-p65 protein expression level in the NF-κB pathway.

Quality of recovery from general anesthesia with remifentanil versus sufentanil:A systematic review / 医学研究生学报

Objective Controversies remain as to the recovery time, recovery quality, and incidence of peri-recovery adverse reactions of the patient receiving general anesthesia with remifentanil and sufentanil.This study aimed to systematically assess the qual-ity of recovery from general anesthesia with remifentanil and sufentanil. Methods Randomized controlled trials ( RCTs) were re-trieved from The Cochrane Library, PubMed, MEDLINE, EMbase, Ovid, Springer, Web of Science, CNKI, CBM, VIP, and Wan-Fang Data.According to the modified Jadad quality scale, the literature retrieved was screened and subjected to quality evaluation and meta-analysis was performed on the included studies using the RevMan 5.1 software. Results Thirty-three RCTs involving 2175 pa-tients were finally included.The results of meta-analysis showed no significant differences between the remifentanil and sufentanil groups undergoing thyroid surgery either in the recovery time to spontaneous breathing ( T1) and eye-opening ( T2) and endortracheal extubation time ( T3 ) ( P >0.05 ) or in the incidence rate of postoperative nausea and vomiting (PONV) (P>0.05).T1, T2 and T3 were significantly shorter in the sufentanil than in the remifentanil group in other types of surgery (P<0.05).The patients with level-1 Ramsay score were remarkably more in the remifentanil than in the sufentanil group ( MD =13.67, 95% CI 2.67 -69.91 ) ( P <0.05), and the VAS scores were markedly higher in the former than in the latter group at 30 minutes (MD=3.37, 95% CI 3.28-3.46) and 1 hour after extubation (MD=2.53, 95% CI 2.43 -2.63) (P<0.05). Conclusion Compared with sufentanil, remifentanil provides a quicker recovery but a weaker analgesia effect and a higher rate of post-operative agitation.However, sufentanil produces a better pain relief and a higher quality of recovery after operation.

Resveratrol facilitates neuropathic pain in rats model by decreasing acetylation of NF-κB p65 / 中国药理学通报

Aim To investigate the antagonistic effect of resveratrol on neuropathic pain and its underlying mechanism. Methods Neuropathic pain was induced by ligation of L5 spinal nerve (SNL) in rats. 90 male Sprague-Dawley rats, fit with intrathecal catheters were divided randomly into six groups ( n = 15 ): naive group; sham group; SNL group; high dosage of res-veratrol group (300μg);middle dosage of resveratrol group ( 30μg ) and low dosage of resveratrol group (3μg). The naive group did not make any process. In sham group, the L5 spinal nerve was only exposed without ligation. Other groups received SNL. Different dosages of resveratrol dissolved in 10μL 100% DMSO were administered by intrathecal injections once a day for 4 days, starting on day 4 after SNL. Paw withdraw-al latency (PWL) was measured on day 1,3,5,7,9, 11,14 days after surgery separately. On day 7 after be-havioral testing, the lumbar segments of the spinal cord were removed to measure the level of SIRT1 and acety-lated-p65(Ac-p65) for western blot. The activation of NF-κB was determined through calculating the percent-age of NF-κB-immunofluorescence positive staining cells in this study. Results Compared with sham groups,the SNL group showed an obvious decrease(P< 0. 05) of PWL and SIRT1 after surgery,whereas Ac-p65 and actived NF-κB significantly increased ( P <0. 05) in the spinal cord. Administration with high and middle dosages of resveratrol markedly attenuated(P <0. 05) SNL-induced thermal hyperalgesia and down-regulation of SIRT1 and blocked (P < 0. 05) the SNL-induced up-regulation of Ac-p65 and actived NF-κB in the spinal cord. Conclusion Intrathecal resveratrol can inhibit the development of neuropathic pain and suppress the activation of NF-κB signaling in SNL rats . The analgesic effect of resveratrol is implemented partly via increasing the level of SIRT1 and deacetylat-ing p65.

Effects of sevoflurane on development of posttraumatic stress disorder in rats and the role of hippocampal GSK-3β / 中华麻醉学杂志

Objective To evaluate the effects of sevoflurane on the development of posttraumatic stress disorder (PTSD) in rats and the role of hippocampal glycogen synthase kinase-3beta (GSK-3β).Methods Forty male Sprague-Dawley rats,weighing 250-300 g,aged 2 months,were randomly divided into 4 groups (n =10 each):control group (group C) ; PTSD group (group P) ; sevoflurane group (group S) ; lithium chloride (LiC1) + sevoflurane group (group LS).Establishment of PTSD model:the rats received 15 footshocks (1 mA,1 s shocks with a variable intershock interval of 240-480 s) in room A on the first day.On the second day,the rats received 1 footshock after an adaptation of 192 s in room B where its context was completely different from room A,and then they were removed from room B 32 s later.The rats were placed in room B and observed for 512 s on the third day.Group C did not receive any treatment on the first day in room A,while the other three groups received 15 footshocks in room A.In addition,0.8％ sevoflurane was administrated while training in group S,and group LS received intraperitoneal LiCl 100 mg/kg at 30 min before entering room A,and then the other treatments were similar to those previously described in group S.The ratio of freezing was recorded in room B on the second and third days.Four rats in each group were randomly sacrificed at 2 h after training in room A on the first day and their hippocampal tissues were taken to detect the expression of GSK-3β and phosphorylated GSK-3β (p-GSK-3β).Results Compared with group C,the ratio of freezing was significantly increased on the third day and the p-GSK-3β expression was up-regulated in P and LS groups,and no significant change was found in the parameters mentioned above in group S.Compared with group P,the ratio of freezing was significantly decreased on the third day and the p-GSK-3β expression was down-regulated in group S,and no significant change was found in the parameters mentioned above in group LS.Compared with group S,the ratio of freezing was significantly increased on the third day and the p-GSK-3β expression was up-regulated in group LS.There was no significant difference in the ratio of freezing on the second day and expression of p-GSK-3β between the four groups.Conclusion Sevoflurane can inhibit the development of PTSD in rats,and enhancement of hippocampal GSK-3β activity may be involved in the mechanism.

Effects of nAChR antagonist α-conotoxin Eb1.6 on thermal pain threshold and spinal astrocytes activa-tion and IL-βexpression in rats using L5 nerve transaction model / 临床麻醉学杂志

Objective To observe the effects of nAChR antagonistα-conotoxin Eb1.6 on ther-mal pain threshold and spinal IL-1βexpression levels and astrocytes activation in rats using L5 spinal nerve transaction (SNT)model.Methods Fifty male Sprague-Dawley rats were randomly assigned into 5 groups with each group 10 rats:sham group,different doses of α-CTX Eb1.6 (0.1 5,1.5 and 1 5 nmol/kg)groups and the saline group after SNT.Saline solution or different doses of Eb1.6 were intraperitoneally injected seven days after the surgery when the model was stable and the treatment continued for seven days.Measured the TWLs of all groups of the rats 1,2,4,7,12 hours after the in-jection on 7 d and 13 d.The rats were sacrificed and L5 spinal cord tissues were collected immediately after the behavioral tests on 13 d.The expression of GFAP and IL-1βwere assessed by Western blot assay and enzyme linked immunosorbent assay (ELISA)separately.Results Groups E1,E2,E3 and C had shorter TWL before the injection on 7 d and 13 d than group N(P <0.05).The TWLs of the rats in groups E1,E2 and E3 of 1 h,2 h and 4 h after the injection on 7 d were significantly higher than that before the injection(P <0.05)with 2 h after the injection showed the most obvious change.The TWL of 1 h,2 h,4 h and 7 h after the injection of the rats in group E1,E2 and E3 and those of 12 h after the injection of the rats in group E2 and E3 on 13 d were significantly higher than that before the injection(P <0.05 )and also higher than TWL of the respective time points on 7 d(P < 0.05 ),also with 2 h after the injection showed the most obvious change.The TWLs of 2 h after the injection a-mong group E1,E2 and E3 showed significant differences both on 7 d and 13 d (P <0.05).Rats spi-nal IL-1βand GFAP expression levels of group E1,E2,E3 and C were significantly higher than those of group N(P <0.05).Rats spinal IL-1β and GFAP expression levels of groups E1,E2,E3 signifi-cantly decreased compared with group C(P <0.05).There were significant differences among the spi-nal IL-1βand GFAP expression levels of group E1,E2 and E3(P <0.05).Conclusion Eb1.6 dose-de-pendently reduced the thermal hyperalgesia induced by L5 spinal nerve transection.Repeated treat-ment of Eb1.6 could produce better analgesic effect,which might be partly attribute to the inhibition of spinal IL-βlevels and astrocytes activation.