Vascular etiology is the second most prevalent cause of cognitive impairment globally.Endothelin-1,which is produced and secreted by endothelial cells and astrocytes,is implicated in the pathogenesis of stroke.However...Vascular etiology is the second most prevalent cause of cognitive impairment globally.Endothelin-1,which is produced and secreted by endothelial cells and astrocytes,is implicated in the pathogenesis of stroke.However,the way in which changes in astrocytic endothelin-1 lead to poststroke cognitive deficits following transient middle cerebral artery occlusion is not well understood.Here,using mice in which astrocytic endothelin-1 was overexpressed,we found that the selective overexpression of endothelin-1 by astrocytic cells led to ischemic stroke-related dementia(1 hour of ischemia;7 days,28 days,or 3 months of reperfusion).We also revealed that astrocytic endothelin-1 overexpression contributed to the role of neural stem cell proliferation but impaired neurogenesis in the dentate gyrus of the hippocampus after middle cerebral artery occlusion.Comprehensive proteome profiles and western blot analysis confirmed that levels of glial fibrillary acidic protein and peroxiredoxin 6,which were differentially expressed in the brain,were significantly increased in mice with astrocytic endothelin-1 overexpression in comparison with wild-type mice 28 days after ischemic stroke.Moreover,the levels of the enriched differentially expressed proteins were closely related to lipid metabolism,as indicated by Kyoto Encyclopedia of Genes and Genomes pathway analysis.Liquid chromatography-mass spectrometry nontargeted metabolite profiling of brain tissues showed that astrocytic endothelin-1 overexpression altered lipid metabolism products such as glycerol phosphatidylcholine,sphingomyelin,and phosphatidic acid.Overall,this study demonstrates that astrocytic endothelin-1 overexpression can impair hippocampal neurogenesis and that it is correlated with lipid metabolism in poststroke cognitive dysfunction.展开更多
OBJECTIVE: To investigate the effects of combined acupuncture and eugenol on learning-memory ability and the antioxidation system of the hippocampus in Alzheimer disease (AD) rats. METHODS: Sixty Sprague Dawley rats, ...OBJECTIVE: To investigate the effects of combined acupuncture and eugenol on learning-memory ability and the antioxidation system of the hippocampus in Alzheimer disease (AD) rats. METHODS: Sixty Sprague Dawley rats, weighing (300±10) g, were randomly divided with 10 rats per group into a normal control group, AD model group, AD with cut olfactory nerve group, Xiu three-needle group, eugenol group, and combined acupuncture and eugenol group. The AD model was established by injection of amyloid β1-40 (Aβ 1-40). Morris maze tests were conducted for evaluating the learning-memory ability. Content of malo- ndialdehyde (MDA) and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the hippocampus were detected. RESULTS: The average escape latency and the mean swimming distance in the normal control group, the Xiu three-needle group, the eugenol group, and the combined acupuncture and euge-nol group were significantly shorter than those in the AD model group (all P<0.01). The combined acupuncture and eugenol group had shorter escape latency and mean swimming distance than those in the Xiu three-needle group and the eugenol group. There were no significant differences between the Xiu three-needle group and the eugenol group and between the AD group and the AD with cut olfactory nerve group (P>0.05). Compared with the normal control group, the MDA content in the hippocampus significantly increased (P<0.05) and GSH-Px and SOD activities significantly decreased in the AD model group (P<0.01). Compared with the AD model group, significantly decreased (P< 0.01) and SOD and GSH-Px activities significantly increased in the Xiu three-needle group, eugenol group, and combined acupuncture and eugenol group (P<0.05). Compared with the Xiu three-needle group and eugenol group, the MDA content significantly decreased (P<0.05) and SOD and GSH-Px activities increased (P<0.05) in the combined acupuncture and eugenol group. There were no significant differences among the three indices between the Xiu three-needle group and the eugenol group and between the AD model group and the AD with cut olfactory nerve group (P>0.05). CONCLUSION: Both Xiu three-needle and eugenol can increase learning-memory ability, decrease MDA content, and increase SOD and GSH-Px activities in the hippocampus in AD rats. The combination of acupuncture with eugenol has stronger effects, and the effects depend on the olfactory pathway.展开更多
Objective:To observe the effect of scalp acupoint cluster needling on learning and memory ability and inflammatory mediators in CA1 area of hippocampus in rats with Alzheimer's disease(AD).Methods:A total of 40 SP...Objective:To observe the effect of scalp acupoint cluster needling on learning and memory ability and inflammatory mediators in CA1 area of hippocampus in rats with Alzheimer's disease(AD).Methods:A total of 40 SPF Wistar rats were randomly divided into blank group,sham operation group,model group and scalp acupoint cluster needling group,with 10 rats in each group.The AD model was duplicated by injecting Abeta 1-42 solution into bilateral hippocampus in model group and scalp acupoint cluster needling group.The sham operation group was injected with the same amount of sterile hydrogen peroxide,while the blank group was not treated.The scalp acupoint cluster needling group was given acupuncture intervention from 2 d after model establishment.The blank group,sham operation group and model group were only bundled and fixed in the dorsal position once a day for 14 consecutive days.After treatment,the learning and memory ability of AD rats was tested by Morris water maze test,the contents and activities of Ach,ChAT and AcE in hippocampal CA1 area were detected by ELISA,and the expressions of IL-6,IL-10 protein and mRNA in hippocampal CA1 area were detected by immunohistochemistry and RT-PCR,respectively.Results:Ach content,ChAT activity,IL-10 protein and mRNA expression in hippocampus were significantly lower than those in blank group,while AchE activity and IL-6 protein and mRNA expression were significantly higher than those in blank group.Compared with the model group,scalp acupoint cluster needling could significantly reduce the escape latency time,increase the number of crossing platforms and effective residence time,increase the content of Ach,the activity of ChAT,the expression of IL-10 protein and mRNA in hippocampus,and decrease the activity of AchE and the expression of IL-6 protein and mRNA.Conclusion:Controlling the expression of inflammatory factors and promoting the content of Ach in hippocampal CA1 region of AD rats can improve the learning and memory ability of AD rats.展开更多
In the present study,Fmr1 knockout mice （KO mice） were used as the model for fragile X syndrome.The results of step-through and step-down tests demonstrated that Fmr1 KO mice had shorter latencies and more error cou...In the present study,Fmr1 knockout mice （KO mice） were used as the model for fragile X syndrome.The results of step-through and step-down tests demonstrated that Fmr1 KO mice had shorter latencies and more error counts,indicating a learning and memory disorder.After treatment with 30,60,90,120,or 200 mg/kg lithium chloride,the learning and memory abilities of the Fmr1 KO mice were significantly ameliorated,in particular,the 200 mg/kg lithium chloride treatment had the most significant effect.Western blot analysis showed that lithium chloride significantly enhanced the expression of phosphorylated glycogen synthase kinase 3 beta,an inactive form of glycogen synthase kinase 3 beta,in the cerebral cortex and hippocampus of the Fmr1 KO mice.These results indicated that lithium chloride improved learning and memory in the Fmr1 KO mice,possibly by inhibiting glycogen synthase kinase 3 beta activity.展开更多
Transthyretin (TTR), a carrier protein present in the liver and choroid plexus of the brain, has been shown to be responsible for binding thyroid hormone thyroxin (T4) and retinol in plasma and cerebrospinal fluid (CS...Transthyretin (TTR), a carrier protein present in the liver and choroid plexus of the brain, has been shown to be responsible for binding thyroid hormone thyroxin (T4) and retinol in plasma and cerebrospinal fluid (CSF). TTR aids in sequestering of beta-amyloid peptides Aβ deposition, and protects the brain from trauma, ischemic stroke and Alzheimer disease (AD). Accordingly, hippocampal gene expression of TTR plays a significant role in learning and memory as well as in simulation of spatial memory tasks. TTR via interacting with transcription factor CREB regulates this process and decreased expression leads to memory deficits. By different signaling pathways, like MAPK, AKT, and ERK via Src, TTR provides tropical support through megalin receptor by promoting neurite outgrowth and protecting the neurons from traumatic brain injury. TTR is also responsible for the transient rise in intracellular Ca2+ via NMDA receptor, playing a dominant role under excitotoxic conditions. In this review, we tried to shed light on how TTR is involved in maintaining normal cognitive processes, its role in learning and memory, under memory deficit conditions;by which mechanisms it promotes neurite outgrowth;and how it protects the brain from Alzheimer disease (AD).展开更多
A case presentation indicating the importance of “happiness” in childhood causing memory block until the patent presented with probable mixed vascular and neurodegenerative memory loss at 60 years of age is presente...A case presentation indicating the importance of “happiness” in childhood causing memory block until the patent presented with probable mixed vascular and neurodegenerative memory loss at 60 years of age is presented to highlight the role of emotional factors in causing the disease. The question of whether Alzheimer’s disease is an adaptability disorder is raised, given the patient blocked out her memory of her childhood experience. The importance of “happiness” as a treatment goal raises issues of advocacy and Guardianship as well as capacity, which is addressed by actual case reference and court action in defence of the patient’s rights to have their wishes respected and observed. Functional mental capacity assessment, using the Functional Mental State Measure (FMSM) gives a greater indication of neuronal reserve than standard cognitive testing, as it helps to unravel the dilemma associated with pure cognitive assessment in Alzheimer’s Disease as well as vascular dementia patients and patients who, despite retained and intact functional capacity and ability to express their wishes, i.e. “best interest”, are “wrongly” placed under Guardianship. Maladaptive responses, to control the change in external environment that are sensed or perceived, and which lead to disorder or to susceptibility to disease, exemplify a General Systems Theory approach, in which appropriate and adequate responses to environmental change, in behavioural terms, by a person, whether independently, or as the recipient or giver, or both, leads to functional interaction and happiness.展开更多
Objective To determine the impact of passive smoking and the protective effect of antioxidants such as vitamin E and quercetin on learning and memory ability of mouse offsprings. Methods A passive smoking model of pre...Objective To determine the impact of passive smoking and the protective effect of antioxidants such as vitamin E and quercetin on learning and memory ability of mouse offsprings. Methods A passive smoking model of pregnant mice was established. Learning and memory ability was evaluated by the water maze test and long term potentiation （LTP）. Nitric oxide （NO）, content, nitric oxide synthase （NOS）, acetylcholinesteras （Ache） activity in brain, vitamin E concentration, and reactive oxygen species （ROS） in serum were determined. The latency period （the time during which the mice swim from the starting position to the ending position） and errors （the number of mice entering the blind end） in control and antioxidant intervention groups were compared with those in the smoke exposure group after 6 days. Results The latency period as well as errors in the air, control diet, tobacco smoke （TS）, and vitamin E diet groups were decreased significantly as compared with the TS and control diet groups （P〈O.05）. LTP was restrained in the TS and control diet groups. LTP in all the antioxidant diet groups was significantly increased compared with the TS and control diet groups. In addition, NOS and acetylcholinesteras （Ache） activitiy was significantly higher in the TS and control diet groups than in the air and control diet group. NO content was not significantly different among the different groups, and significantly lower in the TS and vitamin E diet groups than in the TS group, control diet group, quercetin diet group, and mixture diet group （P〈0.05）. Vitamin E concentration and ROS activity in serum were correlated with the outcome of water maze and LTP. Conclusion Passive smoking reduces LTP formation by disturbing the hippocampus function of mice, by decreasing NOS （especially vitamin E） partially improve the learning and memory smoke during pregnancy. and Ache activity and increasing NO content. Antioxidants ability of offsprings whose mothers are exposed to tobacco展开更多
Clinical reports have demonstrated that the Kongsheng Zhenzhong pill （KSZZP）, a classical prescription deriving from Valuable Prescription for Emergencies, has good therapeutic effects on vascular dementia. However,...Clinical reports have demonstrated that the Kongsheng Zhenzhong pill （KSZZP）, a classical prescription deriving from Valuable Prescription for Emergencies, has good therapeutic effects on vascular dementia. However, the mechanisms that mediate its effects remain unclear. In this study, the expression of N-methyI-D-aspartate receptor 1 mRNA, the content of nitric oxide, and the concentration of calcium in neurons was determined with in situ hybridization, spectrophotometry and flow cytometry, respectively. In addition, the expressions of N-methyI-D-aspartate receptor 1, nerve growth factor protein, and glial cell line-derived neurotrophic factor protein were detected with immunohistochemistry. We found that KSZZP could significantly decrease the expression of N-methyI-D-aspartate receptor 1 mRNA and protein, the content of nitric oxide, and the concentration of calcium in neurons. KSZZP also increased the expression of nerve growth factor and glial cell line-derived neurotrophic factor protein in the hippocampus CA1 region and in the cerebral cortex. Morris water maze and passive avoidance tests verified that KSZZP ameliorated the cognitive impairments of vascular dementia rats. Moreover, the KSZZP-induced improvements in the cognitive functions of vascular dementia rats were correlated with both inhibition of N-methyl-D-aspartate-induced excitable neurotoxicity and elevation of neurotrophic factor expression.展开更多
We studied on the effect of Curcuma longa extract on spatial learning-related memory ability of old rats in eight-arm radial maze task. Rats were randomly divided into two groups: one group was orally administered 100...We studied on the effect of Curcuma longa extract on spatial learning-related memory ability of old rats in eight-arm radial maze task. Rats were randomly divided into two groups: one group was orally administered 100 mg/KgBW/day C. longa extract (CLE) dissolved in deionized water and the other group was administered the vehicle alone for 10 weeks. The rats were tested with the partially baited eight-arm radial maze to evaluate two types of spatial memory-related learning ability displayed by reference memory errors (RMEs) and working memory errors (WMEs). Chronic administration of CLE significantly decreased the number of RMEs and WMEs, concurrently with the decreases in the cortico-hippocampal levels of lipid peroxides (LPO) and tumor necrosis factor alpha (TNF-α). In a parallel set of experiments, CLE-pretreated rats of the same age group were subjected to hypoxia-reperfusion injury by carotid artery occlusion to induce oxidative stress in the brains in order to examine whether such an in vivo hypoxia-induced oxidative stress could be ameliorated by the extract. Again, the levels of LPO were significantly decreased in the cortico-hippocampal tissues of the CLE-fed hypoxic rats. The histology of the brains also revealed that the CLE-pretreated rats had retained improved cellular integrity. Finally, our results provide the evidence that oral administration of C. longa extract increases the defense against oxidative stress and proinflammatory TNF-α, concurrently with the improvement of memory-related brain cognitive ability of the aged rats.展开更多
Optogenetics is a combination of optics and genetics technology that can be used to activate or inhibit specific cells in tissues. It has been used to treat Parkinson’s disease, epilepsy and neurological diseases, bu...Optogenetics is a combination of optics and genetics technology that can be used to activate or inhibit specific cells in tissues. It has been used to treat Parkinson’s disease, epilepsy and neurological diseases, but rarely Alzheimer’s disease. Adeno-associated virus carrying the CaMK promoter driving the optogenetic channelrhodopsin-2 (CHR2) gene (or without the CHR2 gene, as control) was injected into the bilateral dentate gyri, followed by repeated intrahippocampal injections of soluble low-molecular-weight amyloid-β1–42 peptide (Aβ1–42). Subsequently, the region was stimulated with a 473 nm laser (1–3 ms, 10 Hz, 5 minutes). The novel object recognition test was conducted to test memory function in mice. Immunohistochemical staining was performed to analyze the numbers of NeuN and synapsin Ia/b-positive cells in the hippocampus. Western blot assay was carried out to analyze the expression levels of glial fibrillary acidic protein, NeuN, synapsin Ia/b, metabotropic glutamate receptor-1a (mGluR-1a), mGluR-5, N-methyl-D-aspartate receptor subunit NR1, glutamate receptor 2, interleukin-1β, interleukin-6 and interleukin-10. Optogenetic stimulation improved working and short-term memory in mice with Alzheimer’s disease. This neuroprotective effect was associated with increased expression of NR1, glutamate receptor 2 and mGluR-5 in the hippocampus, and decreased expression of glial fibrillary acidic protein and interleukin-6. Our results show that optogenetics can be used to regulate the neuronal-glial network to ameliorate memory functions in mice with Alzheimer’s disease. The study was approved by the Animal Resources Committee of Jinan University, China (approval No. LL-KT-2011134) on February 28, 2011.展开更多
Heat sinks were invented to absorb heat from an electronic circuit conduct, and then to dissipate or radiate this heat to the surrounding supposedly, ventilated space, at a rate equal to or faster than that of its bui...Heat sinks were invented to absorb heat from an electronic circuit conduct, and then to dissipate or radiate this heat to the surrounding supposedly, ventilated space, at a rate equal to or faster than that of its buildup. Ventilation was not initially recognized as an essential factor to thermal dispersion. However, as electronic circuit-boards continued to heat up, circuit failure became a problem, forcing the inclusion of miniaturized high speed fans. Later, heat sinks with fins and quiet fans were incorporated in most manufactured circuits. Now heat sinks come in the form of a fan with fans made to function as fins to disperse heat. Heat sinks absorb and radiate excess heat from circuit-boards in order to prolong the circuit’s life span. The higher the thermal conductivity of the material used the more efficient and effective the heat sink is. This paper is an attempt to theoretically design a heat sink with a temperature gradient lower than that of the circuit board’s excess heat.展开更多
A case presentation indicating the importance of “happiness” in childhood causing memory block until the patent presented with probable mixed vascular and neurodegenerative memory loss at 60 years of age is presente...A case presentation indicating the importance of “happiness” in childhood causing memory block until the patent presented with probable mixed vascular and neurodegenerative memory loss at 60 years of age is presented to highlight the role of emotional factors in causing the disease. The question of whether Alzheimer’s disease is an adaptability disorder is raised, given the patient blocked out her memory of her childhood experience. The importance of “happiness” as a treatment goal raises issues of advocacy and Guardianship as well as capacity, which is addressed by actual case reference and court action in defence of the patient’s rights to have their wishes respected and observed. Functional mental capacity assessment, using the Functional Mental State Measure (FMSM) gives a greater indication of neuronal reserve than standard cognitive testing, as it helps to unravel the dilemma associated with pure cognitive assessment in Alzheimer’s Disease as well as vascular dementia patients and patients who, despite retained and intact functional capacity and ability to express their wishes, i.e. “best interest”, are “wrongly” placed under Guardianship. A General Systems approach, which recognises functional interaction as optimal and withdrawal or inadequate and/or inappropriate response as not, provides further understanding of the relationship between emotional factors, memory and neurodegenerative (Alzheimer’s) disease.展开更多
There are presently no in-depth published neuropsychological studies of West Nile Virus (WNV) encephalitis patients that have been well-correlated with high resolution structural MRI. In this study a middleaged male w...There are presently no in-depth published neuropsychological studies of West Nile Virus (WNV) encephalitis patients that have been well-correlated with high resolution structural MRI. In this study a middleaged male who developed West Nile Virus encephalitis five years previously was examined three times over a two year period. We examined him with the Wechsler Adult Intelligence Scales—Fourth Edition and the Wechsler Memory Scale—Fourth Edition (WAIS-IV/WMS-IV) and Advanced Clinical Solutions battery supplemented by tests of attention, executive, motor and sensory functions. Neuroradiological imaging revealed hypodensities within the left hippocampus in the axial and coronal planes with T2-FLAIR MRI. The man was previously high functioning and although he had prior history of well-controlled epilepsy it seems unlikely that the epilepsy could fully account for the neuropathological changes. The patient had previously completed a demanding six year double science degree program before he became ill with WNV and he had been a successful manager and director of a research company. Delayed auditory memory scores were at least two standard deviation units below age expected levels and semantic fluency and Booklet Category Tests of executive function were also in the impaired range. Moreover the illness onset profile of muscle weakness, extreme fatigue, memory complaints as well as inability to carry out research projects involving planning on the job were highly consistent with WNV encephalitis. If the memory and executive function deficits had been premorbid manifestations of epilepsy it is unlikely he would have attained the levels he did educationally and occupationally. This left hippocampal lesion is characteristic of other encephalitic viral infections such as herpes simplex virus. To our knowledge this is the first lateralized WNV encephalitis medial temporal lobe patient in the published literature.展开更多
Fluoroalkyl end-capped vinyltrimethoxysilane oligomer [RF-(CH2CHSi(OMe)3)n-RF;RF = CF(CF3)OCF7, n = 2, 3;RF-(VM)n-RF] was applied to the preparation of fluoroalkyl end-capped vinyltrimethoxysilane oligomer/α-, β-, ...Fluoroalkyl end-capped vinyltrimethoxysilane oligomer [RF-(CH2CHSi(OMe)3)n-RF;RF = CF(CF3)OCF7, n = 2, 3;RF-(VM)n-RF] was applied to the preparation of fluoroalkyl end-capped vinyltrimethoxysilane oligomer/α-, β-, γ-cyclodextrin polymers (α-, β-, γ-CDPs) composites [RF-(VM-SiO2)n-RF/α-, β-, γ-CDPs] by the sol-gel reaction of the corresponding oligomer in the presence of the α-, β-, γ-CDPs under alkaline conditions. The RF-(VM-SiO2)n-RF/α-, β-, γ-CDPs composites thus obtained were found to give a good dispersibility toward the traditional organic media except for water, and were applied to the surface modification of glass to provide a sueperoleophilic/superhydrophobic characteristic on the modified surface, although the corresponding RF-(VM-SiO2)n-RF nanocomposites can give a usual oleophobic/superhydrophobic property on the surface. These composites powders were also found to be applicable to the packing material for the column chromatography to separate the mixture of oil/water and the water in oil (W/O) emulsions. More interestingly, these composite powders were found to have a higher adsorption ability toward not only low-molecular weight aromatic compounds such as bisphenol A and bisphenol AF but also volatile organic compounds, compared to that of the pristine α-, β-, γ-CDPs.展开更多
Oxidative stress is involved in the pathogenesis of vascular dementia. Studies have shown that lycopene can significantly inhibit oxidative stress;therefore, we hypothesized that lycopene can reduce the level of oxida...Oxidative stress is involved in the pathogenesis of vascular dementia. Studies have shown that lycopene can significantly inhibit oxidative stress;therefore, we hypothesized that lycopene can reduce the level of oxidative stress in vascular dementia. A vascular dementia model was established by permanent bilateral ligation of common carotid arteries. The dosage groups were treated with lycopene(50, 100 and 200 mg/kg) every other day for 2 months. Rats without bilateral carotid artery ligation were prepared as a sham group. To test the ability of learning and memory, the Morris water maze was used to detect the average escape latency and the change of search strategy. Hematoxylin-eosin staining was used to observe changes of hippocampal neurons. The levels of oxidative stress factors, superoxide dismutase and malondialdehyde, were measured in the hippocampus by biochemical detection. The levels of reactive oxygen species in the hippocampus were observed by dihydroethidium staining. The distribution and expression of oxidative stress related protein, neuron-restrictive silencer factor, in hippocampal neurons were detected by immunofluorescence histochemistry and western blot assays. After 2 months of drug administration,(1) in the model group, the average escape latency was longer than that of the sham group, and the proportion of straight and tend tactics was lower than that of the sham group, and the hippocampal neurons were irregularly arranged and the cytoplasm was hyperchromatic.(2) The levels of reactive oxygen species and malondialdehyde in the hippocampus of the model group rats were increased, and the activity of superoxide dismutase was decreased.(3) Lycopene(50, 100 and 200 mg/kg) intervention improved the above changes, and the lycopene 100 mg/kg group showed the most significant improvement effect.(4) Neuron-restrictive silencer factor expression in the hippocampus was lower in the sham group and the lycopene 100 mg/kg group than in the model group.(5) The above data indicate that lycopene 100 mg/kg could protect against the learning-memory ability impairment of vascular dementia rats. The protective mechanism was achieved by inhibiting oxidative stress in the hippocampus. The experiment was approved by the Animal Ethics Committee of Fujian Medical University, China(approval No. 2014-025) in June 2014.展开更多
提出了一种基于最小二乘支持向量机的织物剪切性能预测模型,并且采用遗传算法进行最小二乘支持向量机的参数优化,将获得的样本进行归一化处理后,将其输入预测模型以得到预测结果.仿真结果表明,基于最小二乘支持向量机的预测模型比BP神...提出了一种基于最小二乘支持向量机的织物剪切性能预测模型,并且采用遗传算法进行最小二乘支持向量机的参数优化,将获得的样本进行归一化处理后,将其输入预测模型以得到预测结果.仿真结果表明,基于最小二乘支持向量机的预测模型比BP神经网络和线性回归方法具有更高的精度和范化能力.
Abstract：
A new method is proposed to predict the fabric shearing property with least square support vector machines ( LS-SVM ). The genetic algorithm is investigated to select the parameters of LS-SVM models as a means of improving the LS- SVM prediction. After normalizing the sampling data, the sampling data are inputted into the model to gain the prediction result. The simulation results show the prediction model gives better forecasting accuracy and generalization ability than BP neural network and linear regression method.展开更多
The α5 subunit-containing gamma-amino butyric acid type A receptors(α5 GABAARs) are a distinct subpopulation that are specifically distributed in the mammalian hippocampus and also mediate tonic inhibitory currents ...The α5 subunit-containing gamma-amino butyric acid type A receptors(α5 GABAARs) are a distinct subpopulation that are specifically distributed in the mammalian hippocampus and also mediate tonic inhibitory currents in hippocampal neurons. These tonic currents can be enhanced by low-dose isoflurane, which is associated with learning and memory impairment. Inverse agonists of α5 GABAARs, such as L-655,708, are able to reverse the short-term memory deficit caused by low-dose isoflurane in young animals. However, whether these negative allosteric modulators have the same effects on aged rats remains unclear. In the present study, we mainly investigated the effects of L-655,708 on low-dose(1.3%) isoflurane-induced learning and memory impairment in elderly rats. Young(3-month-old) and aged(24-month-old) Wistar rats were randomly assigned to receive L-655,708 0.5 hour before or 23.5 hours after 1.3% isoflurane anesthesia.The Morris Water Maze tests demonstrated that L-655,708 injected before or after anesthesia could reverse the memory deficit in young rats. But in aged rats, application of L-655,708 only before anesthesia showed similar effects. Reverse transcription-polymerase chain reaction showed that low-dose isoflurane decreased the mRNA expression of α5 GABAARs in aging hippocampal neurons but increased that in young animals. These findings indicate that L-655,708 prevented but could not reverse 1.3% isoflurane-induced spatial learning and memory impairment in aged Wistar rats. All experimental procedures and protocols were approved by the Experimental Animal Ethics Committee of Academy of Military Medical Science of China(approval No. NBCDSER-IACUC-2015128) in December 2015.展开更多
This study aimed to elucidate whether midazolam affected the learning and memory of rats through the extracellular signal-regulated kinase(ERK)/cyclic adenosine monophosphate response element-binding(CREB)signaling pa...This study aimed to elucidate whether midazolam affected the learning and memory of rats through the extracellular signal-regulated kinase(ERK)/cyclic adenosine monophosphate response element-binding(CREB)signaling pathway and hippocampal oxidative damage.Overall 120 Wistar rats were randomly assigned to four groups,including one control and three midazolam-exposed groups(20,60 and 150 mg•kg^(-1)).After an intraperitoneal injection of midazolam/physiological saline for both 1 h(n=15)and 24 h(n=15),10 rats(five came from 1 h,and the remaining five came from 24 h)were randomly selected from each group for the Morris water maze test.The hippocampus tissue samples were harvested for the assessment of superoxide dismutase(SOD)and catalase(CAT)activities as well as glutathione peroxidase(GPx),malonyl dialdehyde(MDA),nitric oxide(NO)and inducible nitric oxide synthase(iNOS)levels.The remaining 80 rats were euthanized,and the hippocampal tissue was isolated.The expressions of ERK1,ERK2 and CREB mRNA were tested using RT-qPCR.The protein expressions of p-ERK1/2 and p-CREB were tested using Western blotting.The Morris water maze tests indicated that midazolam-treated rats have weaker learning and memory ability compared to the control rats.Midazolam increased MDA,NO,iNOS and CAT,and decreased GPx and SOD activities compared to the control group.The expression levels of ERK1/2 and CREB in the hippocampus of rats in the midazolam treatment groups were significantly lower compared to the control group at 1 h after intraperitoneal injection of midazolam,and in a dose-dependent relationship but returning it to normal levels at 24 h after midazolam intraperitoneal injection.Therefore,it was concluded that the learning and memory impairment of midazolam might be associated with the down-regulation of the ERK/CREB signaling pathway and oxidative damage in rat hippocampus.展开更多
BACKGROUND： Patients suffer from changes of cognitive function postoperatively, which has attracted extensive attentions in clinic. It is still to be investigated whether operation damages both antegrade memory and r...BACKGROUND： Patients suffer from changes of cognitive function postoperatively, which has attracted extensive attentions in clinic. It is still to be investigated whether operation damages both antegrade memory and retrograde memory, or either of them. OBJECTIVE： To observe the effects of operation on the anterograde and retrograde memory with Y maze test. DESIGN： A randomly controlled animal trial. SETTING： Department of Anesthesiology, Pudong New Area Gongli Hospital of Shanghai City. MATERIALS： Sixty-three male healthy Sprague-Dawley （SD） rats of clean degree, weighing 200 - 250 g, 10 weeks old, were provided by the animal center of Chinese Academy of Sciences. The rats were tested by antegrade and retrograde respectively. The rats were randomly divided into normal control group （n =7）, anesthesia group （n =14）, sham-operated group （n =14）; partial hepatectomy group （n =14）, short-term retrograde memory group （n =7） and long-term retrograde memory group （n =7）. According to the time of Y maze training started, rats in the anesthesia group, sham-operated group and partial hepatectomy group were observed at 1 and 7 days after anesthesia. METHODS： The experiments were carried out in the central laboratory of Pudong New Area Gongli Hospital of Shanghai City from February to June in 2006. ① Test for antegrade memory： Rats in the normal control group were only treated with intraperitoneal injection of saline without aesthesia and operation; Those in the anesthesia group were anesthetized with intraperitoneal injection of 10 g/L pentobarbital sodium （40 mg/kg）; Those in the sham-operated group were anesthetized, then intraperitoneal exploration was performed without hepatectomy; Those in the partial hepatectomy group were anesthetized, then fixed in a supine position after righting reflex disappeared, and an incision of 1.5 - 2.0 cm was made along the midline of xiphoid lower abdomen, then left lateral lobe of liver （about 1/3 of total liver） was freed, and ligated at distal pedicel with 1^# filament. The abdomen was closed layer by layer after complete hemostasis. The learning and memory abilities were tested after operation. The rats were exposed to Y maze exercise from the 1st or 7th day after surgery, the error numbers, the time to complete whole trials per day and active avoidance numbers were recorded to evaluate the antegrade memory ability. ② Test for short-term retrograde memory Rats in the short-term retrograde memory group were trained in Y maze as the above methods for 1 day, then partial hepatectomy was performed immediately, and the effects on short-term memory were evaluated at 24 hours postoperatively.③ Test for long-term retrograde memory： Rats in the long-term retrograde memory group were trained in Y maze till reached the standard for grasping, then partial hepatectomy was performed in those reached the standard for grasping within 3 days, and the effects on long-term memory were evaluated at 48 hours postoperatively. MAIN OUTCOME MEASURES： The error times, the time to complete whole trials per day and active avoidance times were observed every day. RESULTS： Totally 63 SD rats were used, including 6 failed in the partial hepatectomy in the partial hepatectomy group, 3 died due to over-anesthesia, and 5 in the long-term retrograde memory group grasped the tasks in Y maze till the 4^th day, which were supplemented by other rats. ① Impairment of anterograde memory after partial hepatectomy： The results of Y maze test in the partial hepatectomy group were not obviously different from those in the other groups on the 1st day. The error times on the 2^nd and 3^rd days of training in the partial hepatectomy group at l and 7 days after anesthesia were obviously more than those in the normal control group （F =6.08, P 〈 0.01）, and the active avoidance numbers were obviously fewer than those in the normal control group （F =10.85, P 〈 0.05）; For the rats at 1 day after anesthesia, the error times on the 3^rd day of training in the partial hepatectomy group were obviously more than those in the normal control group （F = 12.34, P 〈 0.01）, and the active avoidance numbers were obviously fewer than those in the normal control group （F =3.91, P 〈 0.05）. There were no obvious differences in the anesthesia group and sham-operated group as compared with those in the normal control group. ② hnpairment of retrograde memory after partial hepatectomy： The results of Y maze test in the normal control group and retrograde short-term memory group at 24 hours after operation were better than those in each group on the 1^st day of training （F=35.22, 22.56, P 〈 0.01）, and the results on the 2nd day had no obvious differences between the two groups. For the rats reached the standards for grasping in the retrograde long-term memory group, the results of Y maze test on the 3rd day of training were obviously better than those on the 1^st day （F-52.38, 43.86, P 〈 0.01）. At 48 hours after operation （the 5^th day of training）, the results of Y maze test in the normal control group and retrograde short-term memory group were still obviously better than those in each group on the 1^st day of training （F=52.38, 43.86, P 〈 0.01）, but there were no obvious differences between the two groups on the 5^th day, CONCLUSION： Partial hepatectomy mainly impaires the anterograde memory abilities of rats, and it has no effect on the retrograde short-term memory and long-term memory.展开更多
基金financially supported by the National Natural Science Foundation of China,No.81303115,81774042 (both to XC)the Pearl River S&T Nova Program of Guangzhou,No.201806010025 (to XC)+3 种基金the Specialty Program of Guangdong Province Hospital of Chinese Medicine of China,No.YN2018ZD07 (to XC)the Natural Science Foundatior of Guangdong Province of China,No.2023A1515012174 (to JL)the Science and Technology Program of Guangzhou of China,No.20210201 0268 (to XC),20210201 0339 (to JS)Guangdong Provincial Key Laboratory of Research on Emergency in TCM,Nos.2018-75,2019-140 (to JS)
文摘Vascular etiology is the second most prevalent cause of cognitive impairment globally.Endothelin-1,which is produced and secreted by endothelial cells and astrocytes,is implicated in the pathogenesis of stroke.However,the way in which changes in astrocytic endothelin-1 lead to poststroke cognitive deficits following transient middle cerebral artery occlusion is not well understood.Here,using mice in which astrocytic endothelin-1 was overexpressed,we found that the selective overexpression of endothelin-1 by astrocytic cells led to ischemic stroke-related dementia(1 hour of ischemia;7 days,28 days,or 3 months of reperfusion).We also revealed that astrocytic endothelin-1 overexpression contributed to the role of neural stem cell proliferation but impaired neurogenesis in the dentate gyrus of the hippocampus after middle cerebral artery occlusion.Comprehensive proteome profiles and western blot analysis confirmed that levels of glial fibrillary acidic protein and peroxiredoxin 6,which were differentially expressed in the brain,were significantly increased in mice with astrocytic endothelin-1 overexpression in comparison with wild-type mice 28 days after ischemic stroke.Moreover,the levels of the enriched differentially expressed proteins were closely related to lipid metabolism,as indicated by Kyoto Encyclopedia of Genes and Genomes pathway analysis.Liquid chromatography-mass spectrometry nontargeted metabolite profiling of brain tissues showed that astrocytic endothelin-1 overexpression altered lipid metabolism products such as glycerol phosphatidylcholine,sphingomyelin,and phosphatidic acid.Overall,this study demonstrates that astrocytic endothelin-1 overexpression can impair hippocampal neurogenesis and that it is correlated with lipid metabolism in poststroke cognitive dysfunction.
基金Supported by a Grant from the National Natural Sciences Foundation of China(No.30973792)
文摘OBJECTIVE: To investigate the effects of combined acupuncture and eugenol on learning-memory ability and the antioxidation system of the hippocampus in Alzheimer disease (AD) rats. METHODS: Sixty Sprague Dawley rats, weighing (300±10) g, were randomly divided with 10 rats per group into a normal control group, AD model group, AD with cut olfactory nerve group, Xiu three-needle group, eugenol group, and combined acupuncture and eugenol group. The AD model was established by injection of amyloid β1-40 (Aβ 1-40). Morris maze tests were conducted for evaluating the learning-memory ability. Content of malo- ndialdehyde (MDA) and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the hippocampus were detected. RESULTS: The average escape latency and the mean swimming distance in the normal control group, the Xiu three-needle group, the eugenol group, and the combined acupuncture and euge-nol group were significantly shorter than those in the AD model group (all P<0.01). The combined acupuncture and eugenol group had shorter escape latency and mean swimming distance than those in the Xiu three-needle group and the eugenol group. There were no significant differences between the Xiu three-needle group and the eugenol group and between the AD group and the AD with cut olfactory nerve group (P>0.05). Compared with the normal control group, the MDA content in the hippocampus significantly increased (P<0.05) and GSH-Px and SOD activities significantly decreased in the AD model group (P<0.01). Compared with the AD model group, significantly decreased (P< 0.01) and SOD and GSH-Px activities significantly increased in the Xiu three-needle group, eugenol group, and combined acupuncture and eugenol group (P<0.05). Compared with the Xiu three-needle group and eugenol group, the MDA content significantly decreased (P<0.05) and SOD and GSH-Px activities increased (P<0.05) in the combined acupuncture and eugenol group. There were no significant differences among the three indices between the Xiu three-needle group and the eugenol group and between the AD model group and the AD with cut olfactory nerve group (P>0.05). CONCLUSION: Both Xiu three-needle and eugenol can increase learning-memory ability, decrease MDA content, and increase SOD and GSH-Px activities in the hippocampus in AD rats. The combination of acupuncture with eugenol has stronger effects, and the effects depend on the olfactory pathway.
基金Scientific Research Project of Heilongjiang Health and Family Planning Commission(2018231).
文摘Objective:To observe the effect of scalp acupoint cluster needling on learning and memory ability and inflammatory mediators in CA1 area of hippocampus in rats with Alzheimer's disease(AD).Methods:A total of 40 SPF Wistar rats were randomly divided into blank group,sham operation group,model group and scalp acupoint cluster needling group,with 10 rats in each group.The AD model was duplicated by injecting Abeta 1-42 solution into bilateral hippocampus in model group and scalp acupoint cluster needling group.The sham operation group was injected with the same amount of sterile hydrogen peroxide,while the blank group was not treated.The scalp acupoint cluster needling group was given acupuncture intervention from 2 d after model establishment.The blank group,sham operation group and model group were only bundled and fixed in the dorsal position once a day for 14 consecutive days.After treatment,the learning and memory ability of AD rats was tested by Morris water maze test,the contents and activities of Ach,ChAT and AcE in hippocampal CA1 area were detected by ELISA,and the expressions of IL-6,IL-10 protein and mRNA in hippocampal CA1 area were detected by immunohistochemistry and RT-PCR,respectively.Results:Ach content,ChAT activity,IL-10 protein and mRNA expression in hippocampus were significantly lower than those in blank group,while AchE activity and IL-6 protein and mRNA expression were significantly higher than those in blank group.Compared with the model group,scalp acupoint cluster needling could significantly reduce the escape latency time,increase the number of crossing platforms and effective residence time,increase the content of Ach,the activity of ChAT,the expression of IL-10 protein and mRNA in hippocampus,and decrease the activity of AchE and the expression of IL-6 protein and mRNA.Conclusion:Controlling the expression of inflammatory factors and promoting the content of Ach in hippocampal CA1 region of AD rats can improve the learning and memory ability of AD rats.
基金the National Natural Science Foundation of China,No.30870876the Natural Science Foundation of Guangdong Province,No.815101700100005+2 种基金the Science and Technology Program of Guangdong Province,No.2005B60302004,2008B030301371,2009B030801368the Traditional Chinese Medicineand Combination of Traditional Chinese and Western Medicine Program of Guangzhou,No.2008A52the Medical and Health Scientific Research Program of Guangzhou,No.2009-YB-167
文摘In the present study,Fmr1 knockout mice （KO mice） were used as the model for fragile X syndrome.The results of step-through and step-down tests demonstrated that Fmr1 KO mice had shorter latencies and more error counts,indicating a learning and memory disorder.After treatment with 30,60,90,120,or 200 mg/kg lithium chloride,the learning and memory abilities of the Fmr1 KO mice were significantly ameliorated,in particular,the 200 mg/kg lithium chloride treatment had the most significant effect.Western blot analysis showed that lithium chloride significantly enhanced the expression of phosphorylated glycogen synthase kinase 3 beta,an inactive form of glycogen synthase kinase 3 beta,in the cerebral cortex and hippocampus of the Fmr1 KO mice.These results indicated that lithium chloride improved learning and memory in the Fmr1 KO mice,possibly by inhibiting glycogen synthase kinase 3 beta activity.
文摘Transthyretin (TTR), a carrier protein present in the liver and choroid plexus of the brain, has been shown to be responsible for binding thyroid hormone thyroxin (T4) and retinol in plasma and cerebrospinal fluid (CSF). TTR aids in sequestering of beta-amyloid peptides Aβ deposition, and protects the brain from trauma, ischemic stroke and Alzheimer disease (AD). Accordingly, hippocampal gene expression of TTR plays a significant role in learning and memory as well as in simulation of spatial memory tasks. TTR via interacting with transcription factor CREB regulates this process and decreased expression leads to memory deficits. By different signaling pathways, like MAPK, AKT, and ERK via Src, TTR provides tropical support through megalin receptor by promoting neurite outgrowth and protecting the neurons from traumatic brain injury. TTR is also responsible for the transient rise in intracellular Ca2+ via NMDA receptor, playing a dominant role under excitotoxic conditions. In this review, we tried to shed light on how TTR is involved in maintaining normal cognitive processes, its role in learning and memory, under memory deficit conditions;by which mechanisms it promotes neurite outgrowth;and how it protects the brain from Alzheimer disease (AD).
文摘A case presentation indicating the importance of “happiness” in childhood causing memory block until the patent presented with probable mixed vascular and neurodegenerative memory loss at 60 years of age is presented to highlight the role of emotional factors in causing the disease. The question of whether Alzheimer’s disease is an adaptability disorder is raised, given the patient blocked out her memory of her childhood experience. The importance of “happiness” as a treatment goal raises issues of advocacy and Guardianship as well as capacity, which is addressed by actual case reference and court action in defence of the patient’s rights to have their wishes respected and observed. Functional mental capacity assessment, using the Functional Mental State Measure (FMSM) gives a greater indication of neuronal reserve than standard cognitive testing, as it helps to unravel the dilemma associated with pure cognitive assessment in Alzheimer’s Disease as well as vascular dementia patients and patients who, despite retained and intact functional capacity and ability to express their wishes, i.e. “best interest”, are “wrongly” placed under Guardianship. Maladaptive responses, to control the change in external environment that are sensed or perceived, and which lead to disorder or to susceptibility to disease, exemplify a General Systems Theory approach, in which appropriate and adequate responses to environmental change, in behavioural terms, by a person, whether independently, or as the recipient or giver, or both, leads to functional interaction and happiness.
文摘Objective To determine the impact of passive smoking and the protective effect of antioxidants such as vitamin E and quercetin on learning and memory ability of mouse offsprings. Methods A passive smoking model of pregnant mice was established. Learning and memory ability was evaluated by the water maze test and long term potentiation （LTP）. Nitric oxide （NO）, content, nitric oxide synthase （NOS）, acetylcholinesteras （Ache） activity in brain, vitamin E concentration, and reactive oxygen species （ROS） in serum were determined. The latency period （the time during which the mice swim from the starting position to the ending position） and errors （the number of mice entering the blind end） in control and antioxidant intervention groups were compared with those in the smoke exposure group after 6 days. Results The latency period as well as errors in the air, control diet, tobacco smoke （TS）, and vitamin E diet groups were decreased significantly as compared with the TS and control diet groups （P〈O.05）. LTP was restrained in the TS and control diet groups. LTP in all the antioxidant diet groups was significantly increased compared with the TS and control diet groups. In addition, NOS and acetylcholinesteras （Ache） activitiy was significantly higher in the TS and control diet groups than in the air and control diet group. NO content was not significantly different among the different groups, and significantly lower in the TS and vitamin E diet groups than in the TS group, control diet group, quercetin diet group, and mixture diet group （P〈0.05）. Vitamin E concentration and ROS activity in serum were correlated with the outcome of water maze and LTP. Conclusion Passive smoking reduces LTP formation by disturbing the hippocampus function of mice, by decreasing NOS （especially vitamin E） partially improve the learning and memory smoke during pregnancy. and Ache activity and increasing NO content. Antioxidants ability of offsprings whose mothers are exposed to tobacco
基金the National Basic Research Program of China(973Program),No.2007CB512601Science and Technology Development Plan of TCM in Shandong Province,No.2009-006Science and Technology Plan in Colleges and Universities of Shandong Province,No.J11LF60,J11LF08
文摘Clinical reports have demonstrated that the Kongsheng Zhenzhong pill （KSZZP）, a classical prescription deriving from Valuable Prescription for Emergencies, has good therapeutic effects on vascular dementia. However, the mechanisms that mediate its effects remain unclear. In this study, the expression of N-methyI-D-aspartate receptor 1 mRNA, the content of nitric oxide, and the concentration of calcium in neurons was determined with in situ hybridization, spectrophotometry and flow cytometry, respectively. In addition, the expressions of N-methyI-D-aspartate receptor 1, nerve growth factor protein, and glial cell line-derived neurotrophic factor protein were detected with immunohistochemistry. We found that KSZZP could significantly decrease the expression of N-methyI-D-aspartate receptor 1 mRNA and protein, the content of nitric oxide, and the concentration of calcium in neurons. KSZZP also increased the expression of nerve growth factor and glial cell line-derived neurotrophic factor protein in the hippocampus CA1 region and in the cerebral cortex. Morris water maze and passive avoidance tests verified that KSZZP ameliorated the cognitive impairments of vascular dementia rats. Moreover, the KSZZP-induced improvements in the cognitive functions of vascular dementia rats were correlated with both inhibition of N-methyl-D-aspartate-induced excitable neurotoxicity and elevation of neurotrophic factor expression.
文摘We studied on the effect of Curcuma longa extract on spatial learning-related memory ability of old rats in eight-arm radial maze task. Rats were randomly divided into two groups: one group was orally administered 100 mg/KgBW/day C. longa extract (CLE) dissolved in deionized water and the other group was administered the vehicle alone for 10 weeks. The rats were tested with the partially baited eight-arm radial maze to evaluate two types of spatial memory-related learning ability displayed by reference memory errors (RMEs) and working memory errors (WMEs). Chronic administration of CLE significantly decreased the number of RMEs and WMEs, concurrently with the decreases in the cortico-hippocampal levels of lipid peroxides (LPO) and tumor necrosis factor alpha (TNF-α). In a parallel set of experiments, CLE-pretreated rats of the same age group were subjected to hypoxia-reperfusion injury by carotid artery occlusion to induce oxidative stress in the brains in order to examine whether such an in vivo hypoxia-induced oxidative stress could be ameliorated by the extract. Again, the levels of LPO were significantly decreased in the cortico-hippocampal tissues of the CLE-fed hypoxic rats. The histology of the brains also revealed that the CLE-pretreated rats had retained improved cellular integrity. Finally, our results provide the evidence that oral administration of C. longa extract increases the defense against oxidative stress and proinflammatory TNF-α, concurrently with the improvement of memory-related brain cognitive ability of the aged rats.
基金supported by the National Natural Science Foundation of China,No.81171191(to LYZ)the Shenzhen Special Fund Project on Strategic Emerging Industry Development of China,No.JCYJ20160422170522075(to LYZ)the Shenzhen Healthcare Research Project of China,No.201601015(to LYZ)
文摘Optogenetics is a combination of optics and genetics technology that can be used to activate or inhibit specific cells in tissues. It has been used to treat Parkinson’s disease, epilepsy and neurological diseases, but rarely Alzheimer’s disease. Adeno-associated virus carrying the CaMK promoter driving the optogenetic channelrhodopsin-2 (CHR2) gene (or without the CHR2 gene, as control) was injected into the bilateral dentate gyri, followed by repeated intrahippocampal injections of soluble low-molecular-weight amyloid-β1–42 peptide (Aβ1–42). Subsequently, the region was stimulated with a 473 nm laser (1–3 ms, 10 Hz, 5 minutes). The novel object recognition test was conducted to test memory function in mice. Immunohistochemical staining was performed to analyze the numbers of NeuN and synapsin Ia/b-positive cells in the hippocampus. Western blot assay was carried out to analyze the expression levels of glial fibrillary acidic protein, NeuN, synapsin Ia/b, metabotropic glutamate receptor-1a (mGluR-1a), mGluR-5, N-methyl-D-aspartate receptor subunit NR1, glutamate receptor 2, interleukin-1β, interleukin-6 and interleukin-10. Optogenetic stimulation improved working and short-term memory in mice with Alzheimer’s disease. This neuroprotective effect was associated with increased expression of NR1, glutamate receptor 2 and mGluR-5 in the hippocampus, and decreased expression of glial fibrillary acidic protein and interleukin-6. Our results show that optogenetics can be used to regulate the neuronal-glial network to ameliorate memory functions in mice with Alzheimer’s disease. The study was approved by the Animal Resources Committee of Jinan University, China (approval No. LL-KT-2011134) on February 28, 2011.
文摘Heat sinks were invented to absorb heat from an electronic circuit conduct, and then to dissipate or radiate this heat to the surrounding supposedly, ventilated space, at a rate equal to or faster than that of its buildup. Ventilation was not initially recognized as an essential factor to thermal dispersion. However, as electronic circuit-boards continued to heat up, circuit failure became a problem, forcing the inclusion of miniaturized high speed fans. Later, heat sinks with fins and quiet fans were incorporated in most manufactured circuits. Now heat sinks come in the form of a fan with fans made to function as fins to disperse heat. Heat sinks absorb and radiate excess heat from circuit-boards in order to prolong the circuit’s life span. The higher the thermal conductivity of the material used the more efficient and effective the heat sink is. This paper is an attempt to theoretically design a heat sink with a temperature gradient lower than that of the circuit board’s excess heat.
文摘A case presentation indicating the importance of “happiness” in childhood causing memory block until the patent presented with probable mixed vascular and neurodegenerative memory loss at 60 years of age is presented to highlight the role of emotional factors in causing the disease. The question of whether Alzheimer’s disease is an adaptability disorder is raised, given the patient blocked out her memory of her childhood experience. The importance of “happiness” as a treatment goal raises issues of advocacy and Guardianship as well as capacity, which is addressed by actual case reference and court action in defence of the patient’s rights to have their wishes respected and observed. Functional mental capacity assessment, using the Functional Mental State Measure (FMSM) gives a greater indication of neuronal reserve than standard cognitive testing, as it helps to unravel the dilemma associated with pure cognitive assessment in Alzheimer’s Disease as well as vascular dementia patients and patients who, despite retained and intact functional capacity and ability to express their wishes, i.e. “best interest”, are “wrongly” placed under Guardianship. A General Systems approach, which recognises functional interaction as optimal and withdrawal or inadequate and/or inappropriate response as not, provides further understanding of the relationship between emotional factors, memory and neurodegenerative (Alzheimer’s) disease.
文摘There are presently no in-depth published neuropsychological studies of West Nile Virus (WNV) encephalitis patients that have been well-correlated with high resolution structural MRI. In this study a middleaged male who developed West Nile Virus encephalitis five years previously was examined three times over a two year period. We examined him with the Wechsler Adult Intelligence Scales—Fourth Edition and the Wechsler Memory Scale—Fourth Edition (WAIS-IV/WMS-IV) and Advanced Clinical Solutions battery supplemented by tests of attention, executive, motor and sensory functions. Neuroradiological imaging revealed hypodensities within the left hippocampus in the axial and coronal planes with T2-FLAIR MRI. The man was previously high functioning and although he had prior history of well-controlled epilepsy it seems unlikely that the epilepsy could fully account for the neuropathological changes. The patient had previously completed a demanding six year double science degree program before he became ill with WNV and he had been a successful manager and director of a research company. Delayed auditory memory scores were at least two standard deviation units below age expected levels and semantic fluency and Booklet Category Tests of executive function were also in the impaired range. Moreover the illness onset profile of muscle weakness, extreme fatigue, memory complaints as well as inability to carry out research projects involving planning on the job were highly consistent with WNV encephalitis. If the memory and executive function deficits had been premorbid manifestations of epilepsy it is unlikely he would have attained the levels he did educationally and occupationally. This left hippocampal lesion is characteristic of other encephalitic viral infections such as herpes simplex virus. To our knowledge this is the first lateralized WNV encephalitis medial temporal lobe patient in the published literature.
文摘Fluoroalkyl end-capped vinyltrimethoxysilane oligomer [RF-(CH2CHSi(OMe)3)n-RF;RF = CF(CF3)OCF7, n = 2, 3;RF-(VM)n-RF] was applied to the preparation of fluoroalkyl end-capped vinyltrimethoxysilane oligomer/α-, β-, γ-cyclodextrin polymers (α-, β-, γ-CDPs) composites [RF-(VM-SiO2)n-RF/α-, β-, γ-CDPs] by the sol-gel reaction of the corresponding oligomer in the presence of the α-, β-, γ-CDPs under alkaline conditions. The RF-(VM-SiO2)n-RF/α-, β-, γ-CDPs composites thus obtained were found to give a good dispersibility toward the traditional organic media except for water, and were applied to the surface modification of glass to provide a sueperoleophilic/superhydrophobic characteristic on the modified surface, although the corresponding RF-(VM-SiO2)n-RF nanocomposites can give a usual oleophobic/superhydrophobic property on the surface. These composites powders were also found to be applicable to the packing material for the column chromatography to separate the mixture of oil/water and the water in oil (W/O) emulsions. More interestingly, these composite powders were found to have a higher adsorption ability toward not only low-molecular weight aromatic compounds such as bisphenol A and bisphenol AF but also volatile organic compounds, compared to that of the pristine α-, β-, γ-CDPs.
基金financially supported by the National Innovation and Entrepreneurship Training Project of China in 2013,No.201310392009(to XZZ)the Innovation and Entrepreneurship Training Project of Fujian Province of China in 2014,No.201410392058(to XZZ)
文摘Oxidative stress is involved in the pathogenesis of vascular dementia. Studies have shown that lycopene can significantly inhibit oxidative stress;therefore, we hypothesized that lycopene can reduce the level of oxidative stress in vascular dementia. A vascular dementia model was established by permanent bilateral ligation of common carotid arteries. The dosage groups were treated with lycopene(50, 100 and 200 mg/kg) every other day for 2 months. Rats without bilateral carotid artery ligation were prepared as a sham group. To test the ability of learning and memory, the Morris water maze was used to detect the average escape latency and the change of search strategy. Hematoxylin-eosin staining was used to observe changes of hippocampal neurons. The levels of oxidative stress factors, superoxide dismutase and malondialdehyde, were measured in the hippocampus by biochemical detection. The levels of reactive oxygen species in the hippocampus were observed by dihydroethidium staining. The distribution and expression of oxidative stress related protein, neuron-restrictive silencer factor, in hippocampal neurons were detected by immunofluorescence histochemistry and western blot assays. After 2 months of drug administration,(1) in the model group, the average escape latency was longer than that of the sham group, and the proportion of straight and tend tactics was lower than that of the sham group, and the hippocampal neurons were irregularly arranged and the cytoplasm was hyperchromatic.(2) The levels of reactive oxygen species and malondialdehyde in the hippocampus of the model group rats were increased, and the activity of superoxide dismutase was decreased.(3) Lycopene(50, 100 and 200 mg/kg) intervention improved the above changes, and the lycopene 100 mg/kg group showed the most significant improvement effect.(4) Neuron-restrictive silencer factor expression in the hippocampus was lower in the sham group and the lycopene 100 mg/kg group than in the model group.(5) The above data indicate that lycopene 100 mg/kg could protect against the learning-memory ability impairment of vascular dementia rats. The protective mechanism was achieved by inhibiting oxidative stress in the hippocampus. The experiment was approved by the Animal Ethics Committee of Fujian Medical University, China(approval No. 2014-025) in June 2014.
文摘提出了一种基于最小二乘支持向量机的织物剪切性能预测模型,并且采用遗传算法进行最小二乘支持向量机的参数优化,将获得的样本进行归一化处理后,将其输入预测模型以得到预测结果.仿真结果表明,基于最小二乘支持向量机的预测模型比BP神经网络和线性回归方法具有更高的精度和范化能力.
Abstract：
A new method is proposed to predict the fabric shearing property with least square support vector machines ( LS-SVM ). The genetic algorithm is investigated to select the parameters of LS-SVM models as a means of improving the LS- SVM prediction. After normalizing the sampling data, the sampling data are inputted into the model to gain the prediction result. The simulation results show the prediction model gives better forecasting accuracy and generalization ability than BP neural network and linear regression method.
文摘The α5 subunit-containing gamma-amino butyric acid type A receptors(α5 GABAARs) are a distinct subpopulation that are specifically distributed in the mammalian hippocampus and also mediate tonic inhibitory currents in hippocampal neurons. These tonic currents can be enhanced by low-dose isoflurane, which is associated with learning and memory impairment. Inverse agonists of α5 GABAARs, such as L-655,708, are able to reverse the short-term memory deficit caused by low-dose isoflurane in young animals. However, whether these negative allosteric modulators have the same effects on aged rats remains unclear. In the present study, we mainly investigated the effects of L-655,708 on low-dose(1.3%) isoflurane-induced learning and memory impairment in elderly rats. Young(3-month-old) and aged(24-month-old) Wistar rats were randomly assigned to receive L-655,708 0.5 hour before or 23.5 hours after 1.3% isoflurane anesthesia.The Morris Water Maze tests demonstrated that L-655,708 injected before or after anesthesia could reverse the memory deficit in young rats. But in aged rats, application of L-655,708 only before anesthesia showed similar effects. Reverse transcription-polymerase chain reaction showed that low-dose isoflurane decreased the mRNA expression of α5 GABAARs in aging hippocampal neurons but increased that in young animals. These findings indicate that L-655,708 prevented but could not reverse 1.3% isoflurane-induced spatial learning and memory impairment in aged Wistar rats. All experimental procedures and protocols were approved by the Experimental Animal Ethics Committee of Academy of Military Medical Science of China(approval No. NBCDSER-IACUC-2015128) in December 2015.
基金Supported by the National Natural Science Foundation of China(32273078)the Applied Technology Research and Development Plan of Heilongjiang Province(GX18B023)。
文摘This study aimed to elucidate whether midazolam affected the learning and memory of rats through the extracellular signal-regulated kinase(ERK)/cyclic adenosine monophosphate response element-binding(CREB)signaling pathway and hippocampal oxidative damage.Overall 120 Wistar rats were randomly assigned to four groups,including one control and three midazolam-exposed groups(20,60 and 150 mg•kg^(-1)).After an intraperitoneal injection of midazolam/physiological saline for both 1 h(n=15)and 24 h(n=15),10 rats(five came from 1 h,and the remaining five came from 24 h)were randomly selected from each group for the Morris water maze test.The hippocampus tissue samples were harvested for the assessment of superoxide dismutase(SOD)and catalase(CAT)activities as well as glutathione peroxidase(GPx),malonyl dialdehyde(MDA),nitric oxide(NO)and inducible nitric oxide synthase(iNOS)levels.The remaining 80 rats were euthanized,and the hippocampal tissue was isolated.The expressions of ERK1,ERK2 and CREB mRNA were tested using RT-qPCR.The protein expressions of p-ERK1/2 and p-CREB were tested using Western blotting.The Morris water maze tests indicated that midazolam-treated rats have weaker learning and memory ability compared to the control rats.Midazolam increased MDA,NO,iNOS and CAT,and decreased GPx and SOD activities compared to the control group.The expression levels of ERK1/2 and CREB in the hippocampus of rats in the midazolam treatment groups were significantly lower compared to the control group at 1 h after intraperitoneal injection of midazolam,and in a dose-dependent relationship but returning it to normal levels at 24 h after midazolam intraperitoneal injection.Therefore,it was concluded that the learning and memory impairment of midazolam might be associated with the down-regulation of the ERK/CREB signaling pathway and oxidative damage in rat hippocampus.
文摘BACKGROUND： Patients suffer from changes of cognitive function postoperatively, which has attracted extensive attentions in clinic. It is still to be investigated whether operation damages both antegrade memory and retrograde memory, or either of them. OBJECTIVE： To observe the effects of operation on the anterograde and retrograde memory with Y maze test. DESIGN： A randomly controlled animal trial. SETTING： Department of Anesthesiology, Pudong New Area Gongli Hospital of Shanghai City. MATERIALS： Sixty-three male healthy Sprague-Dawley （SD） rats of clean degree, weighing 200 - 250 g, 10 weeks old, were provided by the animal center of Chinese Academy of Sciences. The rats were tested by antegrade and retrograde respectively. The rats were randomly divided into normal control group （n =7）, anesthesia group （n =14）, sham-operated group （n =14）; partial hepatectomy group （n =14）, short-term retrograde memory group （n =7） and long-term retrograde memory group （n =7）. According to the time of Y maze training started, rats in the anesthesia group, sham-operated group and partial hepatectomy group were observed at 1 and 7 days after anesthesia. METHODS： The experiments were carried out in the central laboratory of Pudong New Area Gongli Hospital of Shanghai City from February to June in 2006. ① Test for antegrade memory： Rats in the normal control group were only treated with intraperitoneal injection of saline without aesthesia and operation; Those in the anesthesia group were anesthetized with intraperitoneal injection of 10 g/L pentobarbital sodium （40 mg/kg）; Those in the sham-operated group were anesthetized, then intraperitoneal exploration was performed without hepatectomy; Those in the partial hepatectomy group were anesthetized, then fixed in a supine position after righting reflex disappeared, and an incision of 1.5 - 2.0 cm was made along the midline of xiphoid lower abdomen, then left lateral lobe of liver （about 1/3 of total liver） was freed, and ligated at distal pedicel with 1^# filament. The abdomen was closed layer by layer after complete hemostasis. The learning and memory abilities were tested after operation. The rats were exposed to Y maze exercise from the 1st or 7th day after surgery, the error numbers, the time to complete whole trials per day and active avoidance numbers were recorded to evaluate the antegrade memory ability. ② Test for short-term retrograde memory Rats in the short-term retrograde memory group were trained in Y maze as the above methods for 1 day, then partial hepatectomy was performed immediately, and the effects on short-term memory were evaluated at 24 hours postoperatively.③ Test for long-term retrograde memory： Rats in the long-term retrograde memory group were trained in Y maze till reached the standard for grasping, then partial hepatectomy was performed in those reached the standard for grasping within 3 days, and the effects on long-term memory were evaluated at 48 hours postoperatively. MAIN OUTCOME MEASURES： The error times, the time to complete whole trials per day and active avoidance times were observed every day. RESULTS： Totally 63 SD rats were used, including 6 failed in the partial hepatectomy in the partial hepatectomy group, 3 died due to over-anesthesia, and 5 in the long-term retrograde memory group grasped the tasks in Y maze till the 4^th day, which were supplemented by other rats. ① Impairment of anterograde memory after partial hepatectomy： The results of Y maze test in the partial hepatectomy group were not obviously different from those in the other groups on the 1st day. The error times on the 2^nd and 3^rd days of training in the partial hepatectomy group at l and 7 days after anesthesia were obviously more than those in the normal control group （F =6.08, P 〈 0.01）, and the active avoidance numbers were obviously fewer than those in the normal control group （F =10.85, P 〈 0.05）; For the rats at 1 day after anesthesia, the error times on the 3^rd day of training in the partial hepatectomy group were obviously more than those in the normal control group （F = 12.34, P 〈 0.01）, and the active avoidance numbers were obviously fewer than those in the normal control group （F =3.91, P 〈 0.05）. There were no obvious differences in the anesthesia group and sham-operated group as compared with those in the normal control group. ② hnpairment of retrograde memory after partial hepatectomy： The results of Y maze test in the normal control group and retrograde short-term memory group at 24 hours after operation were better than those in each group on the 1^st day of training （F=35.22, 22.56, P 〈 0.01）, and the results on the 2nd day had no obvious differences between the two groups. For the rats reached the standards for grasping in the retrograde long-term memory group, the results of Y maze test on the 3rd day of training were obviously better than those on the 1^st day （F-52.38, 43.86, P 〈 0.01）. At 48 hours after operation （the 5^th day of training）, the results of Y maze test in the normal control group and retrograde short-term memory group were still obviously better than those in each group on the 1^st day of training （F=52.38, 43.86, P 〈 0.01）, but there were no obvious differences between the two groups on the 5^th day, CONCLUSION： Partial hepatectomy mainly impaires the anterograde memory abilities of rats, and it has no effect on the retrograde short-term memory and long-term memory.
