Receptor for advanced glycation end products(RAGE) is a member of the immunoglobulin superfamily.In central nervous system,RAGE is mainly expressed by neurons,microglia,and cerebral endothelial cells.In Alzheimers disease(AD) brain,levels of RAGE are significantly increased from the positive feedback mechanisms driven by excess amounts of ?-amyloid protein(A?).The interaction of RAGE with A? in neurons,microglia,and cerebral endothelial cells induces the perturbation of neuronal functions,amplification of microglia inflammatory responses,and vascular dysfunction.Further understanding the molecular mechanisms associating RAGE-A? interaction provides us the opportunity to develop the therapeutic approaches for the devastating disease.

Objective To study the adriamycin nephrosis model in different development pathological stages. Methods The rat adriamycin nephrosis model was established by injecting adriamycin into tail-vein twice every two weeks to detect blood and urina biochemical indicators and to observe the pathological changes of the renal tissues. Results The model showed serious edema,proteinuria,hypoproteinemia,and hyperlipidemia. Podocytes were swollen and mesangial cells developed mild hyperplasia at the end of the fourth week. The nephric tubule atrophied at the end of the eighth week accompanied with adhesion between glomeruli and Bowman's capsule. Glomeruli sclerosis of mild or medium degree was observed at the end of the twelfth week with obvious lymphocyte infiltration in the renal interstitium as well as the formation of collagen fibers. Conclusion The adriamycin nephrosis model was successfully developed by injecting adriamycin 4 mg/kg into tail-vein twice every two weeks. The acute model is similar to human minimal change disease,and the chronic model is similar to human focal segmental glomerulosclerosis.

Objective To observe the changes in cerebral microcirculation after subarachnoid hemorrhage(SAH) and to study its correlation with cerebral vasospasm(CVS).Methods Eighty-five SAH patients and 35 controls,enrolled in this study as perspective study subjects,were divided into SAH group and control group,CVS group and non-CVS group(nCVS),symptomatic CVS(sCVS) group and asymptomatic CVS(asCVS) group.All the subjects underwent CT perfusion(CTP) and the associated parameters,including cerebral blood flow(CBF),cerebral blood volume(CBV) and mean transit time(MTT),were recorded for final analysis.Results Compared to the control group,the CBF and MTT were significantly changed in SAH group(P

Excessive iron accumulation in the brain occurs in Alzheimer' s disease (AD) with oxidative stress,amyloid deposition,tau phosphorylation,and neuronal cell cycle regulatory failure,leading to apoptosis.Therefore,there is a direct link between iron metabolism and AD pathogenesis. The present review elaborates on high brain iron in etiology of AD and the development of iron-chelating therapy for AD,aiming at preventing or slowing down disease evolution.

Aim To observe the effects of effective fraction of Epimedium,Astragalus,Radix Puerariae on behavioral and pathological changes in a transgenic mouse model of Alzheimer’s disease.Methods Six-month-old APPswe /PS1 ΔE9 transgenic mice were ran-domly divided into 2 groups:model group and effective fraction group,1 0 mice each group.The mice in the effective fraction group were treated with the effective fraction of Astragalus,Radix Puerariae,Epimedium compound for 8 weeks.The C57BL/6J mice were used as negative control group.After 8 weeks,the learning and memory function were measured by Morris water maze,the pathological changes in brain tissue were ob-served by Modified Bielschowsky staining and Nissl 's staining.Results During place navigation trial,the escape latency in the APPswe /PS1 ΔE9 double transgenic model mice was longer than those of the mice of C57 (P <0.05),the escape latency in the mice of effec-tive fraction group was significantly reduced than those of the mice in model group (P <0.05).During spatial probe trail,the platform-crossing times in the APPswe /PS1 ΔE9 double transgenic mice were different from the mice of C57 (P <0.05),the platform-crossing times in the mice of effective fraction group were significantly increased than those of the mice in model group (P <0.05).The average swimming velocity in the APPswe /PS1 ΔE9 double transgenic model mice was increased than that of mice of C57 (P <0.05 ),there was no significant difference between effective fraction group and model group (P > 0.05 ). The Modified Bielschowsky staining shows that the neuron fibers of the cerebral cortex of APPswe /PS1 ΔE9 double transgenic mice were enlarged,swelling,and dense.There were senile plaques and nerve fiber tangles in the cerebral cortex of APPswe /PS1 ΔE9 double transgenic mice.The neuron fibers of mice in the effective fraction group were relieved;there was a small amount of senile plaque.The Nissl’s staining shows that the neurons of the cerebral cortex of APPswe /PS1 ΔE9 mice were edema, the number of cells were decreased.The mice in the effective fraction group were free of the disease.Con-clusion The double transgenic APPswe /PS1 ΔE9 mice of AD can simulate the specific pathogenesis of AD, which may be the efficient experimental animal model. The effective fraction of epimedium,astragalus and ra-dix puerariae may have a neuroprotective effect against AD via improving the learning and memory ability,and reduce the cerebral cortex nerve fiber tangles,senile plaques and neurons edema changes.

OBJECTIVETo study the effect and possible impact mechanism of salidroside on cognitive ability of Alzheimer's disease (AD) model rats induced by amyloid beta peptide (Abeta1-40).

METHODAbeta1-40 was injected into bilateral hippocampus to create the AD model. Afterwards, different doses of salidroside (25, 50, 75 mg x kg(-1)) were orally administered for 21 days. Rats' learning and memory abilities were detected by Morris water maze testing system. The levels of the superoxide dismutase (SOD), malondialdehyde (MDA), and the expression of nuclear factor-kappaB (NF-kappaB), inducible nitric oxide synthase (iNOS) and receptor for advanced glycation end products (RAGE) protein in hippocampus were also detected by different methods.

RESULTThe place navigation test showed longer escape latency, low frequency of platform quadrant crossing per unit time, damage in learning capacity, significant decrease in SOD acivity in hippocampus, notable increase in MDA content, NF-kappaB, iNOS and RAGE protein expressions in rats. Salidroside (50, 75 mg x kg(-1)) significantly alleviated the impairments of learning and memory ability. The activity of SOD increased in salidroside (50 droside group compared with that of the Alzheimer's disease group (P < 0.01).

CONCLUSIONSalidroside may treat Alzheimer's disease by inhibiting the oxidative stress.

Alzheimer Disease ; drug therapy ; Amyloid beta-Peptides ; toxicity ; Animals ; Cognition ; drug effects ; Disease Models, Animal ; Glucosides ; pharmacology ; therapeutic use ; Male ; Maze Learning ; drug effects ; NF-kappa B ; metabolism ; Nitric Oxide ; physiology ; Phenols ; pharmacology ; therapeutic use ; Rats ; Receptor for Advanced Glycation End Products ; Receptors, Immunologic ; analysis ; Superoxide Dismutase ; metabolism

Critical neurosurgery is one of the difficulties and key points in the standardized residency training of neurosurgery. Through the systematic and standardized training of the residents of the Intensive Care Unit of Neurosurgery Department in The First Affiliated Hospital of Chongqing Medical University, consisting of first aid skills training, multi-modal case analysis with complementary theory and practice, expansion of neuroimaging and electrophysiological knowledge, specialized knowledge training in surgical operation and perioperative management, and regular case discussion, their clinical thinking becomes more mature, the time to master the management methods of neurosurgical intensive care patients is significantly shortened, the initiative to participate in clinical practice is also significantly increased, and the perioperative management methods of neurosurgical patients are more deeply understood. These trainings have effectively improved the teaching effect of neurosurgery intensive care unit.

OBJECTIVETo investigate the mechanism of β-amyloid protein (Aβ) in regulating the expression of the receptor for advanced glycation end products (RAGE).

METHODSAβ1-40 was injected into the bilateral hippocampus of rats, and 3 weeks later, the levels of reactive oxygen species (ROS) production were detected by flow cytometry. The expressions of RAGE, reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (gp9l(phox) and p47(phox)), nuclear factor-κB (NF-κB), and inhibitor of κB (IκB) were measured by Western blotting.

RESULTSInjection of Aβ1-40 caused a significant increase in the expressions of RAGE, gp9l(phox), p47(phox), phospho-p47(phox), phospho-IκBα, NF-κB and phospho-NF-κB in rat hippocampus but decreased the level of IκBα. Aβ1-40 injection also resulted in a significantly increased content of ROS in the hippocampus of the rats.

CONCLUSIONAβ up-regulates the expression of RAGE in rat hippocampus via NADPH/ ROS/NF-κB signaling pathway.

Amyloid beta-Peptides ; adverse effects ; Animals ; Hippocampus ; metabolism ; Male ; Membrane Glycoproteins ; metabolism ; NADP ; metabolism ; NADPH Oxidase 2 ; NADPH Oxidases ; metabolism ; NF-kappa B ; metabolism ; Oxidative Stress ; Peptide Fragments ; adverse effects ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species ; metabolism ; Receptor for Advanced Glycation End Products ; Receptors, Immunologic ; metabolism ; Signal Transduction ; Up-Regulation

Objective:To explore the impact of the expression of long noncoding RNA-nuclear-enriched abundant transcript 1 (NEAT1) on neurological function and neuronal apoptosis after traumatic brain injury (TBI) in mice and the possible mechanism.Methods:According to the random number table, 90 C57BL/6J mice were divided into sham group, blank control group, empty virus group 1, empty virus group 2, NEAT1 over-expression group and NEAT1 knockdown group, with 15 mice per group. The traumatic brain injury (TBI) was simulated by controlled cortical injury (CCI) model, and NEAT1 was regulated by intracerebroventricular injection with recombinant adenovirus. The neurological severity score (NSS) and Morris water maze test were used to evaluate the neurological function in blank control group, NEAT1 over-expression group and NEAT1 knockdown group within 1 week and 14-21 days after injury. The Western blot was used to observe the expressions of P53-induced protein with a death domain 1 (Pidd1), caspase-2, caspase-9 and caspase-3 in blank control group at 6 hour and 1, 3, 7 days after injury. The TUNEL method and immunofluorescence were used to observe the neurological apoptosis and expression of Pidd1 in blank control group, NEAT1 over-expression group and NEAT1 knockdown group at 3 days after injury. The Western blot analysis was used to detect protein expressions of Pidd1, caspase-2, cytochrome c (Cyt c) and caspase-3 in sham group, blank control group, empty virus groups, NEAT1 over-expression group and NEAT1 knockdown group at 3 days after injury.Results:The NSS was significantly reduced in NEAT1 over-expression group [(3.5±0.7)points], and was significantly increased in NEAT1 knockdown group [(5.0±1.5)points]at day 1 after injury, when compared with blank control group [(4.9±1.0)points]( P<0.01). The Morris water maze test showed that the time to find platform was decreased in NEAT1 over-expression group[(10.9±2.8)seconds], and was prolonged in NEAT1 knockdown group [(30.7±6.2)seconds] at day 19 after injury ( P<0.05 or 0.01), when compared with blank control group [(20.1±5.6)seconds]. The Western blot analysis showed that the expressions of Pidd1, caspase-2, caspase-9 and caspase-3 had significant increase at day 3 after injury ( P<0.01). The TUNEL test showed that the apoptosis rate of neurons was significantly decreased in NEAT1 over-expression group [(18.0±2.7)%], and the apoptosis rate was significantly increased in NEAT1 knockdown group [(63.0±8.6)%] at day 3 after injury ( P<0.01). Immunofluorescence showed that the expression of Pidd1 protein in cytoplasm of the neurons was decreased in NEAT1 over-expression group [(22.7±2.2)%]( P<0.01), and was increased in NEAT1 knockdown group [(72.7±7.0)%]( P<0.01) at day 3 after injury, when compared with blank control group. The Western blot analysis showed that the expressions of Pidd1, capsase-2, Cyt c and caspase-3 were significantly reduced in NEAT1 over-expression group (0.5±0.0, 0.3±0.0, 0.5±0.0, 0.4±0.0) at day 3 after injury, when compared with blank control group. However, the results were opposite in NEAT1 knockdown group. Conclusion:After TBI, the NEAT1 can reduce the activation of caspase-3 through the Pidd1-caspase-2-Cyt c pathway after TBI, regulate neuronal apoptosis, and ultimately play a protective role in neurological function.