Protective effects of lithium treatment for spatial memory deficits induced by tau hyperphosphorylation in splenectomized rats.

1. Postoperative cognitive dysfunction has become more prevalent in recent years. We used a splenectomized rat model with postoperative spatial learning and memory deficits to investigate the role of tau hyperphosphorylation and glycogen synthase kinase-3ß (GSK-3ß) within the hippocampus. 2. Cognitive function was assessed in a Y-maze 1 day before and 1, 3 and 7 days after surgery. We measured site-specific phosphorylation of hippocampal tau (Thr-205 and Ser-396), GSK-3ß activity and expression of interleukin-1ß (IL-1ß), tumour necrosis factor-α (TNF-α) mRNA and protein as markers of inflammation. We also tested the effects of treatment with lithium chloride (LiCl), a GSK-3ß inhibitor. 3. Splenectomy was associated with learning and memory impairment 3 days later, as well as a rapid and massive hyperphosphorylation of hippocampal tau at Thr-205 and Ser-396, activated GSK-3ß, and increased IL-1ß and TNF-α expression. LiCl completely restored tau hyperphosphorylation to control levels. 4. These data from the splenectomized rat model suggest that inflammatory factors affect tau pathology through the GSK-3ß signalling pathway and that LiCl is a promising treatment for postoperative cognitive deficits.

[Effects of glutamine on changes of nuclear factor-kappa B in acute lipopolysaccharide lung injury: experiment with rats].

OBJECTIVE: To investigate the effects of glutamine on the changes of nuclear factor (NF)-kappaB and lung pathology in acute lung injury. METHODS: Forty SD rats underwent injection of lipopolysaccharide (LPS) 5 mg/kg into the femoral vein, and were randomly divided into 4 equal groups: Group B: undergoing injection of glutamine 0.75 g/kg into the femoral vein 1 h before LPS injection, Group C undergoing injection of glutamine and LPS simultaneously, and Group D undergoing injection of glutamine 1 h after LPS injection, and Group E without glutamine injection. Another 10 rats underwent injection of normal saline to be used as controls (Group A). Four hours after the LPS injection the rats were killed with their lungs taken out RT-PCR was used to detect the level of nuclear factor (NF)-kappaB mRNA expression. ELISA was used to detect the tumor necrosis factor (TNF) - in lung. The activity of superoxide dismutase (SOD) was examined by hydroxylamine method, and the malondialdehyde level was determined by thiobarbituric acid (TBA) method. RESULTS: The lung NF-kappaB mRNA expression levels and TNF- levels of Groups B, C, D, and E were all significantly higher than that of Group A (all P < 0.01). The lung NF-kappaB mRNA expression levels and TNF- levels of Groups C and D were all significantly lower than those of Group B (P < 0.01). However, there were no significant differences in lung NF-kappaB mRNA expression level and TNF- level between Group B and Group E (both P > 0.05). The SOD activity of Group B was significantly lower than that of Group A and the MDA content of Group B was significantly higher than that of Group A (both P < 0.05). The SOD activity levels of Groups C and D were significantly higher than that of Group B and the MDA content of Groups C and D were significantly lower than that of Group B (P < 0.01 or P < 0.05). However there were no significant differences in lung SDD activity and MDA content between Groups B and E (both P > 0.05). Obvious inflammatory changes were seen in the lungs of Groups B and E at the similar extent. Only slight infiltration could be seen in Groups C and D. The lung of Group A was normal. CONCLUSION: Early glutamine administration protects the lung against acute LPS injury. The mechanism may be inhibition of the overexpression of NF-kappaB mRNA.

[Myocardial protection by non-invasive limb preconditioning: the role of nuclear factor kappa-B].

AIM: To investigate a possible role for the transcription factor nuclear factor kappa-B (NF-kappaB) in preconditioning of the heart to ischemia by remote, early protection. METHODS: 48 Wistar rats were randomly divided into three experimental groups. In group I/R, the rats underwent 30 min occlusion of the left anterior descending coronary artery, and 120 min reperfusion. In group PL, the rats underwent four cycles of 5 min occlusion and reperfusion of both hind limbs using a tourniquet before the experiment was continued as in Group I/R. In Group P(L-D), we administered NF-kappaB specific inhibitor, ProDTC 125 mg/kg peritoneally, 15 min before IPG. Infarct size as a percentage of the area at risk was determined by triphenyltetrazolium chloride staining. And another 8 rats in each group were killed and myocardium were stored in liquid nitrogen for the measurement of NF-kappaB mRNA. RESULTS: The myocardial infarct size (IS) was decreased significantly in Group PL compared with group I/R, and the IS/AAR was 34.5% +/- 7.6% and 58.5% +/- 8.5%, respectively ( P < 0.05). The IS/AAR was 54.4% +/- 8.9% in group P(L-D), and there was no significant difference compared with group I/R (P > 0.05). The NF-kappaBmRNA was weaker in P(L) group than that in I/R Group,but is stronger than that in P(L-D) group (P < 0.05). There was almost no expression of NF-kappaB mRNA in P(L-D) group. CONCLUSION: Noninvasive limb IPC is effective in protecting the myocardium from ischemia reperfusion injury. NF-kappaB plays an important role in the mechanism of this acute remote preconditioning.

[Mechanism of the protective effects of noninvasive limbs preconditioning on myocardial ischemia-reperfusion injury].

BACKGROUND: This study aimed at assessing the effect of noninvasive limb preconditioning on myocardial infarct size, and determining whether nitric oxide and neurogenic pathway play an important role in the mechanism of acute remote ischemic preconditioning (IPC). METHODS: Forty Wistar rats were randomly divided into four experimental groups. In Group I, the rats underwent 30-minute occlusion of the left anterior descending coronary artery, and 120-minute reperfusion. In Group PL, the rats underwent four cycles of 5-minute occlusion and reperfusion of both hind limbs using a tourniquet before the experiment was continued as in Group I. In Group PL-N and Group PL-H, we administered L-nitro-arginine methyl ester (L-NAME) 10 mg/kg or hexamethonium chloride 20 mg/kg intravenously, 10 minutes before IPC. Infarct size as a percentage of the area at risk was determined by triphenyltetrazolium chloride staining. RESULTS: There were no statistically significant differences in mean arterial pressure and heart rate among these groups at any time point during the experiment (P>0.05). The myocardial infarct size (IS) was decreased significantly in Group PL and Group PL-H compared with Group I, and the IS/AAR was 34.5%+/-7.6%, 35.9%+/-8.6% and 58.5%+/-8.5%, respectively (P< 0.05). The IS/AAR was 49.1%+/- 6.5% in Group PL-N, and there was no significant difference compared with Group I (P>0.05). CONCLUSIONS: Noninvasive limb IPC is effective in protecting the myocardium from ischemia reperfusion injury. Nitric oxide plays an important role in the mechanism of acute remote IPC, in which the neurogenic pathway is not involved.