Objective:To investigate the influence of edaravone on expression of VEGF,IL-1? and TNF-? in vascular cognitive impairment brain and the serum level of VEGF,IL-1? and TNF-? in vascular cognitive impairment rats,in order to study neuroprotection mechanism of edaravone against vascular cognitive impairment.Methods:The vacsular cognitive impairment rat model was established by permanent bilateral occlusion of both common carotid arteries.Behaviour was evaluated 2 weeks after permanent bilateral occlusion of both common carotid arteries with Morris water maze and shuttle box task.Wistar rats were randomly divided into sham-operation group(S),vascular cognitive impairment model group(M)and edaravone treatment group(MT).Serum level and expression of IL-1? and TNF-? was measured by enzyme linked immunosorbent assay,VEGF by enzyme linked immunosorbent assay and western blotting.Results:Edaravone significantly improved cognitive impairment from permanent bilateral occlusion of both common carotid arteries.The serum level and expression of IL-1? and TNF-? in MT group were lower than these in M group(P

Objective To incubate the rat neural stem cells with specific inhibitor (PD98059) of MAPKK/MEK to clarify the effect of MAPKK/MEK-MAPK/ERK signaling pathway in neural stem cells (NSC).Methods NSCs derived fiom E15-16 rats were isolated and cultured.After treated with different concentration of PD98059,they were subjected to the detection of cell proliferation,Nesn'n, BrdU and β-tubulin-Ⅲ by WTS-8 assay,immunofluorescent staining or Western Blot respectively.Results PD98059 had an effect on the survival,proliferation and differentiation of NSC at a concentration-dependent manner.The viability of the NSC was significantly decreased than the control (P＜0.05),whereas the numbers of BrdU-positive and β-tubulin-Ⅲ positive cells were notably fewer than the control (P＜0.05) after incubated with the higher concentration of PD98059.The ERK expression was blocked by PD98059 at a concentration-dependent manner.Conclusion The MAPKK/MEK-MAPK/ERK signaling pathway played a vital role in the survival, proliferation and differentiation of NSC.

Objective To investigate the effect of phosphatidylinesitol-3 kinase/serine threonine kinase (PI3K/Akt) signaling pathway on expression of beta-site amyloid precursor protein cleaving enzyme-1 (BACE1) in the hippocampus neurons of rat brain. Methods Forty SD rats were randomly divided into 4 groups: blank control group, sham-operated group, insulin group and wortmannin group. Insulin or the specific inhibitor of PI3K, wortmannin was injected into hippocampus neurons to activate or inhibit the signaling pathway in insulin group or wortmannin group, respectively. Immunoprecipitation and Western blot were used to analyze the proteins levels of PI3K/Akt and BACE1. Results In insulin treatment group,among the proteins downstream of signaling pathway, expression of Akt increased (0. 952±0.060 vs 0.835±0.029,t=4.9150, P=0.0001), phospho-Akt set473 increased (0.800±0.075 vs 0.657± 0.025,t=4.5598, P=0.0002), phospho-GSK-3α decreased (0.604±0.062 vs 0.726±0.041, t= 3.5871, P=0.0018 ), and the expression of mature BACE1 and β-CTF significantly decreased. In wortmannin group, the expression of Akt and phospho-Akt ser473 were inhibited; phospho-GSK-3α increased ; mature BACEI (1.004±0.096) and β-CTF (1.031±0.048) increased (t=11.5980, P= 0.0000 and t =4.2194, P =0.0004, respectively). Conclusions PI3K/Akt signaling pathway might effect the expression of BACE1, in which impaired signaling pathway may cause the amyloid precursor protein to be easily processed by BACE1, and thus involves the pathology of Alzheimer' s disease.

Objective To investigate expression of β-site APP-cleaving enzymel(BACE1) and Aβ in brain of diabetes mellitus of Wistar rats,to study pathophysiological mechanism of Alzheimer disease from diabetic metabolic disorder. Methods Animal model of diabetes mellitus was established by streptozocin with intraperitoneal injection. Wistar rats were randomly divided into normal group (N), sham-operation group (S), 4 weeks diabetes mellitus model group (M4), 6 weeks diabetes mellitus model group (M6) and 8 weeks diabetes mellitus model group (M8). Behaviour was tested with Morris water maze and shuttle box test. Expression of Aβ was measured by enzyme linked immunosorbent assay and BACE1 by immunohistochemistry, enzyme linked immunosorbent assay, Western blotting and RT-PCR. The absorbance value was measured by imaging analysis. Results The electric times and latancy of memory and study were more increased in model group than that in N and S group but the times of escape more decreased(P<0.01). The expression of Aβ_(1-40) increased from (64.13±6.76)pg/mg in normal group to (86.43±7.03)pg/mg in model group by ELISA(P<0.001) and Aβ_(1-42) from (67.43±5.12 )pg/mg in normal group to (89.45±5.28) pg/mg (P<0.001) in model group. The expression of BACE1 increased from (116.46±8.10)pg/mg in normal group to (158.73±6.24)pg/mg in model group by ELISA and from 0.61±0.11 in normal group to 1.52±0.16 by Western blotting absorbance valule and from 1.62±0.26 in normal group to 3.61±0.32 by RT-PCR absorbance valule and from 0.81±0.21 in normal group to 2.01±0.36 by immunohistochemistry absorbance valule (P<0.001). The expression of BACE1 and Aβ in MT group was higher than that of in N and S group (P<0.01). The level of BACE1 and Aβ had positive correlation with cognitive impairment.Conclusion The expression of BACE1 and Aβ is increased in diabetes mellitus rats. Diabetes mellitus contributes to Alzheimer diseases that.

Poststroke recrudescence (PSR) is a reappear phenomenon in the neurological symptoms of chronic stroke in the setting of toxic metabolic factors. Infection, hyponatremia, and use of benzodiazepine are important precipitants. In this paper, the risk factors, pathogenesis, clinical characteristics, diagnosis and treatment methods of PSR are reviewed to enhance the understanding of the disease among clinicians.