ABSTRACT
Aim To investigate the effect of ASX (trans-astaxanthin)on the expressions of NF-κB p65 , iNOS and TNF-αin the hippocampus and the prefron-tal cortex of chronic alcohol mice.Methods 40 mice were randomly divided into control group,7 d,14 d, 21 d,28 d alcohol-treated group,the mice were given alcohol preference testing on day of 6,13,20,27. Mice were subjected to alcohol withdrawal for one day after testing.In order to determine the exact time point of cognitive memory impairment in mice after alcohol consumption,they were given morris water maze test after alcohol preference testing. The other 40 mice were randomly divided into control group, alcohol group and ASX group (20,40,80 mg·kg-1 ).After chronic ASX administration, mice were given one probe trial of 60 s in which the platform was removed from the pool to evaluate escape latency,the number of times the animal crossed the previous location of the platform,time spent in the target quadrant,and swim-ming speed.The expressions of NF-κB p65 ,iNOS and TNF-αwere detected by western blotting after behav-ioral testing.Results The mice showed an obvious al-cohol-related phenomenon on 2 1 and 28 days after al-cohol treatment,and escape latency significantly in-creased,entries in target quadrant and duration in tar-get quadrant significantly decreased with increasing drinking days and withdrawal times.The results also suggested that 2 1 days chronic ASX treatment reversed this learning deficit.Moreover,the expression of NF-κB p65 ,iNOS and TNF-αin the hippocampus were significantly increased after 2 1 d alcohol treatment (P<0.001),and pretreatment with ASX (40,80 mg· kg-1 ) could obviously inhibit these changes (P <0.001);Parallel to these changes in the hippocam-pus,the level of NF-κB p65 ,iNOS and TNF-αwere also increased in the prefrontal cortex (P<0.001 ), however,only ASX (80 mg · kg-1 ) administration could inhibit the increase (P<0.05 ).Conclusion These results indicate that ASX pretreatment can pro-tect against alcohol-induced memory impairment via the inhibition of NF- κB p65 ,iNOS and TNF-αexpres-sions in hippocampus and prefrontal cortex.
ABSTRACT
Objective To evaluate the effect of long?time mechanical ventilation on early postoper?ative inflammatory responses in the hippocampi of mice. Methods Forty?eight healthy male C57BL∕6 mice, aged 8-10 weeks, weighing 20-25 g, were divided into 3 groups ( n=16 each) using a random number table: control group ( group C) , operation group ( group O) and long?time mechanical ventilation after operation group ( group MV) . Open reduction and internal fixation was performed after tibial fracture was induced in O and MV groups. Group O inhaled isoflurane for 6 h after operation. The mice were me?chanically ventilated for 6 h under isoflurane anesthesia in group MV. On 1 and 3 days after the end of ven?tilation, 8 mice were randomly selected, and contextual fear conditioning test was carried out to assess the cognitive function. The rate of time spent freezing was calculated. Then venous blood samples were collected and hippocampi removed for determination of the levels of interleukin?6 ( IL?6) , tumor necrosis factor?al?pha ( TNF?α) and IL?1β in plasma and hippocampal tissues by enzyme?linked immunosorbent assay. Re?sults Compared with group C, the rate of time spent freezing was significantly decreased, and the levels of IL?6, TNF?α and IL?1β in plasma and hippocampal tissues were significantly increased after the end of ventilation in group O ( P<0.01) . Compared with group O, the rate of time spent freezing was significantly decreased, and the levels of IL?6, TNF?α and IL?1β in plasma and hippocampal tissues were significantly increased after the end of ventilation in group MV ( P<0.01) . Conclusion The mechanism by which long?time mechanical ventilation leads to early postoperative cognitive dysfunction is related to induction of in?flammatory responses in the hippocampi of mice.
ABSTRACT
Objective To observe the expression of discs large hom olog 4 (DLG4) protein in hippocam-pus, am ygdala and frontal cortex of rats and evaluate postsynaptic density in heroin dependence. Meth-ods The rat heroin dependent m odel was established by increasing intraperitoneal injection of heroin. DLG4 proteins in hippocam pus, am ygdala and frontal cortex of heroin dependent 9, 18, 36 days rats w ere detected with im munohistochem ical staining and com pared with that in the control group. Results DLG4 proteins in hippocam pus, am ygdala and frontal cortex w ere gradually reduced with extension of heroin dependent tim e. Conclusion Heroin dependence can affect postsynaptic density of hippocam pus, am ygdala and frontal cortex. The changes becom e m ore apparent with extension of heroin dependence tim e.
ABSTRACT
Objective To evaluate the effect of isoflurane or sevoflurane inhalation before and after gestation on the offspring brain development. Methods Thirty female adult Sprague Dawley rats were randomly assigned into 5 groups(n=6 each):control group(group C),group that ex?posed to isoflurane with the concentration of 1.6%for 6 hours before gestation(group BI),group that exposed to isoflurane with the concentration of 1.6%at the 6th,10th,14th and 18th day for 6 hours(group PI),group that exposed to sevoflurane with the concentration of 2.4%for 6 hours before gestation(group BS),and group exposed to sevoflurane with the concentration of 2.4%at the 6th,10th,14th and 18th day for 6 hours after gestation (group PS). Twelve offspring rats from pregnant rats in each group were chosen on the day of birth(T1),and 7th,14th and 28th days after birth(T2, T3 and T4)and sacrificed,and the hippocampi were then isolated. Hematoxylin and eosin stain were adopted to observe the tissue pathological change. Electron microscope was used to observe the neuron ultrastructure change of hippocampus. Immolunohistochemistry was used to detect cas?pase?3,the expression of growth associated protein?43(GAP?43)and neuronal nitric oxide synthase(nNOS). Results Compared with group C, no significant change was found in caspase?3,GAP?43 and nNOS expression in offspring rat hippocampus in groups BI and BS(P>0.05),and no damage change in hippocampal was seen by HE staining and electron microscopy. In group PI and PB,the expression of caspase?3 was significantly up?regulated,the expression of GAP?43 and nNOS was down?regulated at T1 to T3(P<0.01),and structural changes in cell were seen by electron microscopy. In group PI,significant pathological changes in hippocampal were seen by HE staining at T1 to T3. Compared with group PI,the expres?sion of GAP?43 and nNOS was significantly up?regulated(P<0.01),and the expression of caspase?3 was down?regulated at T1 to T3(P<0.01). Conclusion Isoflurane or sevoflurane inhalation before gestation does not affect the offspring brain development,while isoflurane or sevoflurane in?halation after gestation can induce transient abnormal change of offspring brain development,and isoflurane′s toxicity was greater than sevoflurane.
ABSTRACT
Aim To explore the effects and mecha-nisms of choro-oxime derivatives on spatial learning and memory impairment in Kunming mice and SD rats induced by scopolamine and Aβ1-42 , respectively. Methods 40 Kunming mice were randomly divided into 5 groups: control group, model group, donepezil treatment group, arimoclomol treatment group and TCO-2 treatment group. There were 8 mice in each group. Mice of control group were established by intra-peritoneal injection of saline, and mice of other groups were injected with scopolamine and caused memory im-pairment. Both control group and model group were treated with solvent by intraperitoneal administration;donepezil treatment group received donepezil by intra-gastric administration; arimoclomol treatment group and TCO-2 treatment group were given the correspond-ing drugs by abdominal injection, respectively. The solvent and drugs were given at the same time every morning for 8 days. Spatial learning and memory abili-ty were tested by Morris water maze from the fifth day of the drugs administration. 40 SD rats were divided into 5 groups the same as the dementia model men-tioned above. Mice of control group were established by intracerebroventricular injection of saline, and mice of other groups were injected with insoluble Aβ1-42 to be induced of memory impairment. Solvent and drugs were also delivered as mentioned above. Morris water maze was carried out from the fifth day of the drug de-livery. After that, acetyl cholinesterase activity of hip-pocampus was tested with acetyl cholinesterase reagent kit; the content of Aβ1-42 in hippocampus was meas-ured by ELISA assay kit;the expression of phosphoryl-ated tau proteins was detected by Western Blot. Re-sults In both two dementia models, choro-oxime de-rivatives could improve the spatial learning and memory ability, shorten the escape latency and increase the times of crossing the former platform. Choro-oxime de-rivatives could also inhibit the acetyl cholinesterase ac-tivity in animal brain, decrease the concentration of Aβ1-42 and the expression of phosphorylated tau pro-teins in the dementia rats’ hippocampus. Conclusions Spatial learning and memory deficits induced by sco-polamine and Aβ1-42 could be reversed by choro-oxime derivatives. It may be concerned with enhancement of the cholinergic system functions and reduction of the levels of Aβ1-42 and phosphorylated tau proteins in the brain.
ABSTRACT
Objective To investigate the mechanism of brain derived neurotrophic factor (BDNF) regulated by differ-ent isoforms of tyrosine kinase receptor B (TrkB) in epileptic hippocampal neurons. Methods Primary hippocampal neu-rons were cultured in vitro for 7 days, and divided into two groups, ALLN (calcineurin inhibitor) group and Anisomycin (trans-lation inhibitor) group. ALLN group included control group, control+BDNF group, epilepsy group, epilepsy+BDNF group, control+ALLN group, epilepsy+ALLN group and epilepsy+ALLN+BDNF group. Anisomycin group was sub-divided into con-trol group, control+BDNF group, epilepsy group, epilepsy+BDNF group, control+Anisomycin group, epilepsy+Anisomycin group and epilepsy+Anisomycin+BDNF group. The immunofluorescent technique was used to identificate the hippocampal neurons. Epileptiform discharges were detected by electrophysiological techniques. Western blot assay was used to deter-mine the protein expression of TrkB and phosphorylated TrkB (p-TrkB) in all cell groups. Results (1) In ALLN group, the gray value of p-TrkB/TrkB was higher in control+BDNF group compared with that of control group, the value was higher in epilepsy+BDNF group than that of epilepsy group but was lower than that of control+BDNF group. The gray value of p-TrkB/TrkB was lower in epilepsy+ALLN+BDNF group than that of epilepsy+BDNF group, but no significant difference compared with that of epilepsy+ALLN group. (2) In Anisomycin group:the gray value of p-TrkB/TrkB was higher in control+BDNF group than that of control group. The gray value of p-TrkB/TrkB was higher in epilepsy+BDNF group than that of epilepsy group, but which was lower than that of control+BDNF group. The gray value of p-TrkB/TrkB was higher in epilepsy+Aniso-mycin+BDNF group than that of epilepsy+BDNF group and epilepsy+Anisomycin group. Conclusion The decreased ex-pression of TrkB.T can improve the inhibition of BDNF/TrkB signaling, and BDNF can activate BDNF/TrkB signal pathway in epileptic hippocampal neurons. The increased TrkB.FL protein level by ALLN can’t improve the inhibition of BDNF/TrkB signal pathway.