Objective To study the protective effect on transient focal cerebral ischemic preconditioning against neuronal cell apoptosis again,and the relationship between bcl 2, bax and cerebral ischemic tolerance.Methods Middle cerebral artery occlusion (MCAO) was showed for 20 min by craniotomy and MCA was blocked 6 h after 3 d.Cerebral infarct volume and the change of histopathological in rats were observed,the status of neuronal cell apoptosis were observed by TUNEL mothod,the alteration of bcl 2 and bax protein expression were observed by immunohistochemical method.Results As compared with the false preconditioning group and ischemia group,the infarct volume in the ischemic group reduced significantly after preconditioning( P

Objective To investigate the protective role of transient focal ischemic precondition(PC) against permanent focal cerebral ischemia, to define the proper time dose for precondition, and to study the reaction of astroglia in cerebral ischemic tolerance. Methods Temporary middle cerebral artery occlusion(10 minutes, 20 minutes, 30 minutes) followed three day reperfusion before permanent middle cerebral artery occlusion(PMCAO) transcranially was used as precondition in Wistar rats. The protective role was evaluated by observing the neurological deficits, analyzing the infarct volume and studying changes of pathohistology. The reaction of astroglia was observed by using anti GFAP immunohistochemistry.Results Compared with the control group, 20 min ischemic precondition, which did not produce neuronal damage obviously, alleviated the neurological deficits and reduced the infarct volume significantly( P

This study is to investigate the protective effect of rosiglitazone (RSG) against learning and memory impairment of APP/PS1/tau transgenic mice. AD mice model was replicated by using 6-month APP/PS1/tau transgenic mice. The learning and memory ability of mice was evaluated by Morris water maze and Western blotting assays was applied to measure the phosphorylation and O-glycosylation of Tau and neurofilaments (NFs) protein. The results demonstrated that RSG could reverse the learning and memory deficits of 3 x Tg mice significantly. It was also found that RSG could suppress the hyperphosphorylation of Tau and NFs protein levels and increase the glycosylation expression of Tau and NFs proteins in 3 x Tg mice brain. Together, RSG ameliorates cognitive impairments of 3 x Tg mice via the alleviation of the hyperphosphorylated Tau and NFs proteins burden in the brain.

AIM: To explore the effect of nuclear factor-?B (NF-?B) on the anti-apoptosis induced by brain ischemia preconditioning (IP). METHODS: Temporary middle cerebral artery occlusion for 20 min followed three days reperfusion before 6 hours middle cerebral artery occlusion (MCAO) trancranially was used as preconditioning in Wistar rats. The protective role was evaluated by analyzing the infarct volume. The status of neuronal apoptosis was observed by TUNEL. The expression of NF?B p65 protein, the assay of SOD activity and MDA concentration were analyzed by using the methods of immunohistochemistry and cytochemistry. RESULTS: Compared to the control group, 20 min ischemic preconditioning, which did not produce neuronal damage obviously, reduced the infarct volume significantly after MCAO 6 h and obviously decreased the number of neural cell apoptosis in penumbra (P

Objective To explore the differences between patients withchronic mountain sickness (CMS) and healthy people in the microstructure of brain gray and white matter by using diffusion kurtosis imaging (DKI). Methods 21 CMS patients were recruited to a study group and 20 healthy volunteers were assigned to a control group. Both groups received conventional MRI and DKI sequence scans. The mean kurtosis (MK) values ,radial kurtosis (RK) values and kurtosis anisotropy (KA) values in each region of interest (ROI) in the cerebral gray and white matter were measured and the same part of the left and right side ROI parameters was counted. The data satisfied the normal distribution and the paired samples t?test was used;the ROI parameters between the two groups in the same parts of the same side followed the normal distribution and the two independent samples t?test was used. Results The KA values in both sides of the anterior limb of internal capsule ,the MK values and RK values in bilateral caudate nucleus head and thalamus had side difference in CMS group. In both sides of the anterior limb of the internal capsule′s MK values,KA values and thalamus′s MK values,RK values existed side difference in the control group. The KA values of the right anterior limb in internal capsule were lower than those in the left in both groups;the right thalamus′s MK values and RK values were higher than the other side. The RK value in genu of corpus callosum differed significantly ,and it was lower the CMS group than in the control group. The difference of the KA values in corpus callosum ,the MK value in the left anterior limb of internal capsule ,the RK values in the left posterior limb of internal capsule ,the MK values in the right caudate nucleus head ,the MK values in bilateral lenticular nucleus and the MK values and KA values in the right thalamus were significant ,and they were higher inthe CMS group than in the control group. Conclusions The left and right cerebral hemispheric micro?structure is not exactly symmetrical between patients with CMS and healthy people living in high altitude areas , there are differences in some brain areas. The sensitivity and reactivity of brain tissue to high altitude hypoxia are different in patients with CMS ,there are various degrees of difference between the CMS and the normal in the corpus callosum,basal ganglia region and thalamus.

Aim To study ethanol-induced changes in the development and neuronal number of visual cortex in C57BL /6 mice. Methods Female mice were fed with ethanol during pregnancy . The neuron density (ND) and cortical thickness (CT) in visual cortex of off spring mice were measured at either P0, P7 and P14 with hematoxylin and eosin (H.E) and Nissl staining. Results Embryonic death and malformationswere found in the ethanol-treated groups. Malformations, such as microcephaly,anencephaly and myeloschisis with spinabifida, etc were found in late-term embryos. The malformation rate was 12%. Compared with control group, the development of visual cortex in ethanol-treated groups was delayed, and its lamination was in disorder. The neuron polarity was disturbed. Neuron loss was found after ethanol exposure. At various ages, the neuron density in ethanol-treated groups was lower than that in control group(P

Objective To study ethanol-induced the neuroapoptosis of visual cortex in offspring mice. Methods Pregnant female mice were fed by intubating alcohol daily,beginning on E5(embryonic,E) and continuing through the pup's birth.The neuroapoptosis in P0,P7 and P14 visual cortex was visualized by Caspase-3 activity immunohistochemistry and Terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling(TUNEL) staining. Results Usually,the pup's birth days would delay one or two days after ethanol exposure.Moreover,ethanol induced reabsorption of fetus and malformations,such as microcephaly,anencephaly and myeloschisis with spinabifida and so on,were found in the study.Apoptosis index in ethanol treatment groups was obviously higher than that in control at either P0,P7 or P14(P

Objective To investigate the effects of type 2 diabetes on learning and memory of APP/PS1/Tau triple transgenic (3 × Tg) mice of Alzheimer’s disease, and the protective mechanism of liraglutide (LIR) thereof. Methods One month old C57BL/6 mice were set to be control group (WT). One month old 3×Tg mice were divided into control group (Tg), liraglutide group (Tg+LIR), type 2 diabetes group (Tg+T2DM) and liraglutide treatment group (Tg+T2DM+LIR). The model of T2DM was established by feeding the high fat and sugar fodder, and then injecting streptozotocin (STZ) in mice, making sure the fasting blood glucose was more than 7 mmol/L. Then the subcutaneous injection of LIR was administered for 2 months. The values of body weight and fasting blood glucose were detected at age of 5-month. Morris water maze was applied to evaluate the spatial learning and memory ability. Western blotting assay was used to measure the levels of phosphorylated Tau, neurofilament (NFs) and insulin receptor substrates. ELISA was used to detect the human Aβ42 to evaluate the effect of LIR on-amyloid. Results LIR can reduce body weight and blood glucose, can alleviate spatial learning and memory damaging caused by T2DM, and also can improve phosphorylated Tau levels, NFs and insulin receptor substrates caused by T2DM, and finally can reduce the deposition ofβ-amyloid of 3 × Tg mice. Conclusion T2DM can aggravate symptoms of AD in 3×Tg mice, and LIR has a protective effect on it.

Objective:To evaluate the relationship between intestinal mucosal mast cells and intestinal flora during intestinal ischemia-reperfusion(I/R) in mice.Methods:Forty-eight healthy male C57BL/6 mice, aged 9-12 weeks, weighing 20-25 g, were divided into 4 groups ( n=12 each) using a random number table method: sham operation group (group Sham), sham operation plus mast cell membrane stabilizer cromolyn sodium (CS) group (group Sham+ CS), I/R group and I/R+ CS group.The intestinal I/R injury was induced by clamping the superior mesenteric artery for 45 min followed by 4 h of reperfusion in I/R and I/R+ CS groups.The superior mesenteric artery was only exposed but not occluded in Sham and Sham+ CS groups.CS 50 mg/kg was intraperitoneally injected once a day for two weeks before surgery in Sham+ CS and I/R+ CS groups.The equal volume of normal saline was intraperitoneally injected once a day for two weeks before surgery in Sham and I/R groups.Mice were then sacrificed and intestinal tissues were harvested for examination of the pathological changes of intestinal mucosa with a light microscope after HE staining, and the damage to intestinal tissues was assessed and scored according to Chiu.The expression of mast cell tryptase was detected using the immunohistochemical SP staining method, and the mast cells were counted.The intestinal contents were collected, the total amount of bacteria in intestinal flora was detected by 1% agarose gel electrophoresis, and the diversity (Chao1 index and Shannon index) and relative abundance of intestinal microbial bacteria were detected by 16S rDNA sequencing method. Results:Compared with Sham group, the Chiu′s score and mast cell count were significantly increased, the expression of mast cell tryptase was up-regulated, the total amount of intestinal flora bacteria was increased, Chao1 index and Shannon index were decreased, the relative abundance of Bacteroidetes, Proteobacteria, Bacteroides and Enterobacteriaceae were increased, and the relative abundance of Firmicutes, Lactobacillus and Bifidobacteria was reduced in I/R group ( P<0.05 or 0.01), and no significant change was found in the parameters mentioned above in Sham+ CS group ( P>0.05). Compared with I/R group, the Chiu′s score and mast cell count were significantly decreased, the expression of mast cell tryptase was down-regulated, the total amount of intestinal flora bacteria was decreased, Chao1 index and Shannon index were increased, the relative abundance of Bacteroidetes, Proteobacteria, Bacteroides and Enterobacteriaceae were reduced, and the relative abundance of Firmicutes, Lactobacillus and Bifidobacteria was increased in I/R+ CS group ( P<0.05 or 0.01). Conclusion:The activation of intestinal mucosal mast cell can lead to imbalance of intestinal flora, decrease the number of probiotics and increase the number of potential pathogenic bacteria, and thus be involved in the pathophysiological mechanism of intestinal I/R injury in mice.

Objective To explore the protective effects of dipeptidyl peptidase-4 inhibitor (DPP-4I) on AD-like neurodegenerative changes and its mechanism. Methods The human neuroblastoma cell line SH-SY5Y on the logarithmic phase was divided into six groups:control group (CON group, treated with PBS contained 1‰DMSO for 12 h), wortmannin intervention group (W group, treated with 0.03 μmol/L wortmannin for 12 h), DPP-4I intervention group (DPP-4I group, treated with 10μmol/L DPP-4I for 12 h), both DPP-4I and wortmannin intervention group (DPP-4I+W group, pre-treated with 10 μmol/L DPP-4I for 2 h, then 0.03 μmol/L wortmannin for 12 h), DPP-4I, wortmannin and Ex9-39 intervention group (DPP-4I+W+Ex9-39 group, pre-treated with 10μmol/L Ex9-39 for 2 h, then 10μmol/L DPP-4I for 2 h followed by 0.03μmol/L wortmannin for 12 h), and Ex9-39 intervention group (Ex9-39 group, treated with 10μmol/L Ex9-39 for 12 h). MTT assay was used to detect the cell vitality. Western blot assay was used to detect the level of total tau protein (tau-5) and phosphorylated tau at different sites (pSpS199/202, pT231 and pS396), the level of phosphorylated neurofilaments (NF-H, NF-M) and phosphorylation of critical enzyme in PI3K/Akt/GSK-3β signaling pathway. Results (1) The cell vitality decreased, the levels of pSpS199/202, pT231, pS396 and NF-H/M increased significantly in W group than those in CON group. However, comparing with CON group, the above mentioned parameters reversed in DPP-4I group. Comparing with W group, the cell vitality increased and phosphorylated levels of above mentioned indices were decreased in DPP-4I+W group. (2) The cell vitality showed a decline trend while the levels of phosphorylation tau at three different sites and NF-H/M were higher in Ex9-39 group than those in CON group. Comparing with DPP-4I+W group, the results of the phosphorylated levels showed the same changes in DPP-4I+W+Ex9-39 group. (3) Comparing with CON group, the expression levels of phosphorylated PI3K, Akt and GSK3β increased significantly in DPP-4I group, while those decreased in W group. Additionally, the expression levels of phosphorylated PI3K, Akt and GSK3β were significantly increased in DPP-4I+W group than those in W group. Conclusion DPP-4I can enhance the level of GLP-1 and activate PI3K/Akt/GSK-3βinsulin signaling pathway to improve the hyperphosphorylated tau and NFs induced by wortmannin, and to protect AD-like neurodegeneration.