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Low and high frequency transcutaneous electrical acupoint stimulation are differentiated by their effects on μ-opioid receptors in brain

Low and high frequency transcutaneous electrical acupoint st...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Xiao-Hui XIANG~(1,3),Ying-Mao CHEN~2,Jin-Ming ZHANG~2,Jia-He TIAN~2,Ji-Sheng HAN~1,Cai-Lian CUI~(1,*) 1 Neuroscience Research Institute and Department of Neurobiology,Peking University Health Science Center,Key Laboratory of Neuroscience,the Ministry of Education and Ministry of Public Health,Beijing 100191,China 2 Department of Nuclear Medicine,the Chinese PLA General Hospital,Beijing 100853,China 3 Department of Physiology and Pathophysiology,Medical College of Chinese People's Armed Police Forces,Tianjin 300162,China

Objective Accumulated data show that the mechanisms of transcutaneous electrical acupoint stimulation （TEAS）analgesia involve the activation of endogenous opioid antinociceptive systems and theμ-opioid receptors （MORs）in the central nervous system（CNS）.Positron emission tomography（PET）is the only real time in vivo method available today to study u-opioid receptor *** this study we investigated the different effects of low and high frequency TEAS on MOR binding potential of the brains in rhesus *** PET with C-carfentanil was performed three times randomly under TEAS of 0 Hz,2 Hz or 100 Hz respectively in each monkey separated by at least 2 *** was administered in the middle 30 min during the 95 min PET *** images were reconstructed in 3D OSEM *** distribution volume of three stages（before,during and after TEAS）were calculated using Logan plot with an online arterial radiocounting as input function and were analyzed using Statistical Parametric Mapping（SPM）.Results 2 Hz TEAS evoked an increases in MOR binding potential in multiple pain and sensory processing brain regions including the dorsal cingulated cortex,caudate nucleus,putamen,temporal lobe, somatosensory cortex and amygdale during the TEAS compared with that of 0 Hz *** effect remained after TEAS in genual anterior cingulate cortex and temporal *** increase in MOR binding potential was found during and after the 100 Hz TEAS compared with 0 Hz *** The increases of u-opioid receptor binding potential in multiple pain and sensory processing brain regions may play a role in mediating the effect of low,but not high frequency TEAS.

关键词： μ-opioid receptor positron emission tomography transcutaneous electrical acupoint stimulation

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Roles of dopamine D2 receptor in the sleep-wake regulation

Roles of dopamine D2 receptor in the sleep-wake regulation

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Wei-Min QU~(1,*),Zhi-Li HUANG~(1,2,3) 1 Department of Pharmacology,2 State Key Laboratory of Medical Neurobiology,Shanghai Medical College,3 Institute of Brain Science,Fudan University,Shanghai,200032,China

Dopamine（DA） is critically involved in regulating processes responsible for the generation of complex movements and emotions,cognition,reward processing,and drug *** contrast,the role assigned to DA in sleep-wake regulation has been relatively limited,because the activity of DA neurons in the ventral tegmental area and substantia nigra pars compacta is not significantly modulated by the sleep-wake *** main DA receptors（R） in the brain are DR and *** clarify the roles of DA receptors in the sleep-wake regulation,we used DR knockout （KO） mice and pharmacological *** found that the DR blockade could reduce the sleep latency and increase amounts of non-rapid eye movement（NREM） sleep（Qiu,et *** Biochem Behav 2009）.Modafinil is the most potent wake-promoting medicine for enhancing the extracellular DA level in the nucleus accumbens and the prefrontal cortex,and for increasing wakefulness in *** using DR KO mice and DR antagonist,we demonstrated that DR and DR are essential for the arousal effect of the wake promoting drug modafinil,with DR being the receptor of primary importance（Qu et al.J Neurosci 2008）.Compared with wild-type（WT） mice,DR KO mice exhibited a significant decrease in wakefulness,with a concomitant increase in NREM and REM sleep and a drastic decrease in the low-frequency（0.75-2 Hz） electroencephalogram delta power of NREM sleep,especially during the first 4 h after lights *** the KO mice were subjected to a cage change,the latency to sleep in the KO mice decreased to half of the level for WT *** DR antagonist raclopride mimicked these effects in WT mice. When GBR12909,a DA transport inhibitor,was administered intraperitoneally,it induced wakefulness in WT mice in a dose-dependent manner,but its arousal effect was attenuated to one-third in the DR KO mice（Qu et al.J Neurosci 2010）.These results indicate that DR plays an essential role in the maintenance of wakefulness.

关键词： Roles of dopamine D2 receptor in the sleep-wake regulation

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Behavioral changes induced by Escitalopram treatment in helpless rats

Behavioral changes induced by Escitalopram treatment in help...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Bing LI~1,Na YUE~1,Qiong LIU~2,Yang LIU~1,Jin YU~1,Gen-Cheng WU~(1,3,*) 1 Department of integrative medicine and neurobiology,State key lab of medical neurobiology,Shanghai medical college,Fudan University,Shanghai 200032,China 2 Department of Anatomy,Histology and Embryology,Shanghai medical college,Fudan University,Shanghai 200032, China 3 Institutes of brain science,Fudan University,Shanghai 200032,China

Objective Depression is a severe illness and the prevalence increased gradually in the past decades according to large epidemiological ***,it is crucial to prevent the onset of the disease and approach effective *** aim of the present study was to examine whether Escitalopram treatment can cause antidepressant-like effect and behavior changes in helpless rats,rat models of *** 76 male SD rats were randomly divided into 5 groups:normal(n = 11),model(n = 11),depression + Saline(n = 10),depression + Escitalopram(n = 8),and depression + Clomipramine(as positive control,n = 11).On 2 consecutive days,rats were exposed to 60 inescapable electric foot-shocks(IS).Escape-avoidance behavior was evaluated 3 days after *** that failed to escape between 10 and 30 trials were considered "helpless".Then Escitalopram and Clomipramine treatments were given to helpless rats twice daily(intraperitoneal injection) at the dose of 10 mg/kg for 5 d starting on the evening of the third day after *** medication,the escape-avoidance behavior was evaluated *** depressive-like behaviors were evaluated before IS,after IS and treatment with drug in forced swimming and open field test through the *** As for the number of escape failures in the active avoidance task,the one-way ANOVA indicated a significant effect of treatment with escitalopram(F = 69.28,P<0.01).After inescapable footshock, helpless rats displayed significantly increased escape failure *** expected,helpless rats treated with escitalopram and clomipramine displayed decreased number of escape failures,as compared with helpless rats(F = 17.05,P<0.01). The open field test is a test of spontaneous motor activity for *** inescapable shook,the total distance of travel (F = 29.36,P<0.01) of helpless rats was significantly decreased in the *** escitalopram and clomipramine treatment,the total distance of travel(F= 8.79,P<0.01) of medication-treated rats signi

关键词： Behavioral changes induced by Escitalopram treatment in helpless rats

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Neuropeptide S promotes active waking through activation of histaminergic and orexinergic neurons

Neuropeptide S promotes active waking through activation of ...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Peng ZHAO,Yu-Feng SHAO,Min ZHANG,Kun FAN,Xiang-Pan KONG,Yi-Ping HOU~* Department of Neuroscience,Anatomy,Histology and Embryology,Key Laboratory of Preclinical Study for New Drugs of Gansu Province,School of Basic Medical Sciences,Lanzhou University,Lanzhou 730000,China

Objective The effect of neuropeptide S(NPS) on characteristics and mechanisms in the regulation of sleep-waking cycle are unclear,though the initial findings that NPS promotes arousal associated to locomotor activity and a genuine anxiolytic-like action have recently been *** hypothesized that NPS activated posterior hypothalamic arousal systems involved histaminergic(HAergic) neurons in tuberomammilary nucleus(TMN) and orexinergic(OXergic) neurons in perifornical(PeF) and lateral hypothalamic(LH) area,where NPSR mRNA has been reported to be highly expressed,to regulate sleep-wakefulness *** present studies were designed to provide more information regarding the NPS-induced sleep-waking characteristics and potential targets in posterior hypothalamus by analyzing each state across sleep-waking cycle,especially focusing on active waking(aW) and quiet waking(qW) states since the rather unique behavioral profile challenges the common idea that anxiolytics are also sedative or that stimulants are also anxiogenic,during the 24 h period after a range dose of NPS intracerebroventricular (ICV) injection and by observing earlier genes c-fos *** Four stainless-steel screws as electroencephalogram(EEG) electrodes were screwed into the animals skull and three silver wire as electromyogram (EMG) electrodes were inserted into the dorsal cervical neck muscles to monitor the sleep-wake cycle,and the EEG and EMG signals were amplified and digitalized with a resolution of 256 and 128 Hz respectively using a CED 1401 MKⅡ.After sleep-waking recording,c-fos immunereactive(Fos-IR),histidine decarboxylase(HDC)-IR,orexin-A (OX-A)-IR,and dual labeling of Fos-IR+HDC-IR and Fos-IR+OX-A-IR neurons were respectively labeled to identify the active sites in the brain for the NPS effects on *** The sleep-wake profile after an ICV injection of NPS at 10:00 h was examined,when rats with saline injection spend most of their time in *** given at 0.1 and

关键词： neuropeptide S sleep-wake states EEG power spectra immunohistochemistry histamine orexin

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Baby's,female's,male's faces in my brain——gender differences

Baby's,female's,male's faces in my brain——gender differenc...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Li-Jun YIN~(1,2),Ming-Xia FAN~3,Zhao-Xin WANG~(1,2,3,*) 1 Key Laboratory of Brain Functional Genomics(Ministry of Education),Institute of Cognitive Neuroscience,East China Normal University,Shanghai 200062,China 2 Department of Psychology,School of Psychology and Cognitive Science,East China Normal University,Shanghai 200062,China 3 Shanghai Key Laboratory of MRI,East China Normal University,Shanghai 200062,China

Background Romantic love and parental love are essential to the perpetuation of ***, previous studies focus on mothers' brain responses to their own child or gender differences in brain responses to attractiveness of both *** is known about the gender differences among neural mechanisms of viewing novel faces of infants,ordinary looking female adults and male *** this study,we used fMRI approach to address this *** Sixteen female and sixteen male participants were asked to view infant,female adult and male adult faces with ***,and to give attractiveness ratings for all faces during fMRI *** hundred and eighty infant faces(which were divided into five levels based on cuteness),18 male adult faces,and 18 female adult faces were used as *** Infant faces of high cuteness levels were rated as more attractive than that of low cuteness *** was neither a significant main effect of gender nor a significant interaction between gender and infant cuteness *** 1 infant faces were not significantly different from female and male adult *** participants' attractiveness ratings to female faces were significantly higher than ratings to male faces while male participants' ratings were ***,imaging data showed a complex pattern.(1) Males showed greater activation in the right superior frontal gyrus and right middle frontal gyrus to female adult faces than infant faces,greater activation in the bilateral middle occipital gyrus to infant faces than male adult faces,and greater right nucleus accumbens activation to female adult faces than male adult faces.(2) Only in female participants can we find linear increase in activation with increasing attractiveness ratings for infant faces in right ventral striatum and left orbital frontal *** faces evoked greater activation in left anterior insula and left anterior cingulated cortex while compared male participants with femal

关键词： face gender differences fMRI

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Paeoniflorin produces antidepressant-like effects in behavioral models of depression

Paeoniflorin produces antidepressant-like effects in behavio...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Hua-Cheng YAN~(1,3),Hong-Hai HU~1,Jie ZHANG~1,Liang-Ping LI~1,Xiong CAO~1,Li-Rong SUN~1,Chun-Hua YUAN~1, Hong-Da QU~2,Tian-Ming GAO~1,Xin-Hong ZHU~(1,2,*) 1 Department of Neurobiology,2 School of Traditional Chinese Medicine,Southern Medical University,Guangzhou 510515,China. 3 Department of Pharmacy,Guangzhou General Hospital of Guangzhou Military Command,Guangzhou 510010, China.

Paeoniflorin(PF) is the major bioactive constituent of peony root,which has been used to treat depressive patients in Traditional Chinese ***,whether or not PF has antidepressant effects,and if so,what may be the underlying mechanism,remain *** main goal of the present work was to evaluate the antidepressant effects of PF(i.p.) in various rodent animal models of depression,including the forced swimming test(FST),the novelty-suppressed feeding(NSF) test and the chronic mild stress(CMS) paradigm,and its possible mechanisms underlying the behavioral *** results show that acute PF treatment significantly decreases the total time of immobility in the FST,and the latency in the NSF test is also decreased after 7-d PF injection in adult *** effects are also observed 7 d after PF administration and last up to 1 ***,2-week administration of PF (1.0 mg/kg per day) reverses the anhedonia in rats exposed to a 7-week CMS *** this respect,the effect of PF was similar to the effect of imipramine(20 mg/kg per day),and even showed more rapid onset of action than them. In addition,our findings demonstrate that there are more newborn cells in the hippocampus in PF-treated animals, and most of them are differentiated into ***,acute PF treatment significantly increases BDNF and VEGF expression in the ***,these results suggest that PF is able to enhance adult neurogenesis and produce rapid onset of antidepressant-like effects,while BDNF or/and VEGF signaling may be involved in the mechanism of the antidepressant effect of PF.

关键词： paeoniflorin antidepressant neurogenesis BDNF VEGF

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A novel strategy for partial functional recovery of completely transected lower thoracic spinal cord of adult rats

A novel strategy for partial functional recovery of complete...

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中国神经科学学会第九届全国学术会议暨第五届会员代表大会

作者： Ting-Rao ZHAO Guo-Hua WANG Jian-Quan ZHENG Dong-Hua TIAN San-Jun HU Shu-Qian JING Shao-Jun LIU Shi-De LIN Xiao-Jun ZHANG Shu-Guang YANG Fan-Wen KONG Zheng YONG Fang-Jin CHEN Zhao-Qing LIU Hai-Ping QUE Department of Spinal Cord Repair Jinan General Hospital 25 Shifan Road Jinan 250031 China Department of Neurobiology and State Key Laboratory of Proteomics Institute of Basic Medical Sciences 27 Taiping Road Beijing 100850 China Beijing Institute of Pharmacology and Toxicology 27 Taiping Road Beijing 100850 China Department of Neurobiology and State Key Laboratory of Proteomics Institute of Basic Medical Sciences 27 Taiping Road Beijing 100850 China Department of Neurobiology and State Key Laboratory of Proteomics Institute of Basic Medical Sciences 27 Taiping Road Beijing 100850 China School of Social Development and Public Policy Beijing Normal University 19 Xinjiekou Wai St.Beijing 100875 China Institute of Neuroscience The Fourth Military Medical University Xian 710032 China Department of Neurobiology and State Key Laboratory of Proteomics Institute of Basic Medical Sciences 27 Taiping Road Beijing 100850 China School of Social Development and Public Policy Beijing Normal University 19 Xinjiekou Wai St.Beijing 100875 China Department of Spinal Cord Repair Jinan General Hospital 25 Shifan Road Jinan 250031 China Department of Spinal Cord Repair Jinan General Hospital 25 Shifan Road Jinan 250031 China

Completely transected rat lower thoracic spinal cord was bridged either immediately or lingeringly by microsurgically linking T7 intercostal nerves to L3 dorsal root stumps to establish a bridged *** surgical sites were treated locally with a neurotrophin/growth factor *** the surgery, partial hind limb locomotion and visceral function were gradually *** nerve fibers were then traced to pass through linking sites, grow into L3 dorsal root stumps, enter the spinal cord and eventually contact with neurons in the gray matter of the spinal cord between L2 and *** bridged nerves could trigger evoked potentials in sciatic nerve, bladder, and colon, and induce hind limb *** the bridged nerves transected, the evoked potentials and hind limb locomotion disappeared, urinary retention and feces incontinence occurred *** observations demonstrate that physical and functional linkages between the segments of injured spinal cords have been established by bridging *** is first evidence that the peripheral nerves grow into the central nerve *** importantly, this innovative strategy is potentially applicable for clinic.

关键词： spinal cord injury novel strategy functional recovery neurotrophin/growth factor cocktail

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Transplantation of Olig2-expressing neural stem cells and adoptive immunotherapy of Myelin basic protein activated T cells promotes remyelination and functional recovery after spinal cord injury

Transplantation of Olig2-expressing neural stem cells and ad...

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中国神经科学学会第九届全国学术会议暨第五届会员代表大会

作者： Jian-Guo HU Jian-Sheng ZHOU Yu-Xin ZHANG Bao-Ming ZHAO Shan-Feng MA He-Zuo LV Department of Clinical Laboratory Science The First Affiliated Hospital of Bengbu Medical College Bengbu 233004 China Center Laboratory The First Affiliated Hospital of Bengbu Medical College Bengbu 233004 China Anhui Key Laboratory of Tissue Transplantation Bengbu Medical College Bengbu 233004 China Anhui Key Laboratory of Tissue Transplantation Bengbu Medical College Bengbu 233004 China Center Laboratory The First Affiliated Hospital of Bengbu Medical College Bengbu 233004 China Center Laboratory The First Affiliated Hospital of Bengbu Medical College Bengbu 233004 China

Neural stem cell transplantation is a major focus of current research in treatment of spinal cord injury (SCI).However, it is very important to promote the transplanted neural stem cells (NSCs) differentiate into OLs and neurons in lesion *** previous studies have shown that Olig2-overexpression can promote the differentiation of cultured NSCs into mature ***, it has been reported that myelin basic protein activated T cells (MBP-T) can produce neurotrophic factors, improve the SCI local micro-environment, and be neuroprotective to residual myelin and ***, we suppose that combination of Olig2-modified NSC transplantation and MBP-T cell adoptive immunotherapy may have complementary roles in the treatment of *** this study, the MBP-T cells, which can express IFN-γ, IL-10, and IL-13 after activation in vitro, were passively immunized to spinal cord injured rats within one day after *** NSCs, which were infected with lentivirus expressing green fluorescent protein (GFP-NSCs) or Olig2 (Olig2-GFP-NSCs), were transplanted into injured spinal cord 9 d after *** fate of transplanted cells was tracked by GFP fluorescence after transplantation in different time *** adoptive immunotherapy, the transferred MBP-T cells (CD4-positive) could be detected in injured spinal cord from 3 d to 4 *** infiltration of the MBP-T cells was correlated with and the differentiation of resident microglia and/or infiltrating blood monocytes toward an "alternatively-activated" anti-inflammatory (M2) macrophage *** 2 to 7 weeks after transplantation, the grafted NSCs could be detected to survive and integrate into the injured spinal *** 2 weeks, the survival of grafted NSCs increased fivefold in MBP-T cell-transferred rats compared with vehicle-treated *** engrafted GFP-NSCs mostly differentiated into astrocytes, but not OLs and ***, the percentage of MBP-positive OLs increased 12-fold in Olig2-GFP-NSC-engr

关键词： spinal cord injury passive immunization Olig2 neural stem cells transplantation

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Neuronal nitric oxide synthase alteration accounts for the role of 5-HT1A-receptor in modulating anxiety-related behaviors

Neuronal nitric oxide synthase alteration accounts for the r...

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中国神经科学学会第九届全国学术会议暨第五届会员代表大会

作者： Jing ZHANG Dong-Ya ZHU Xin-Yan HUANG Min-Li YE Chun-Xia LUO Hai-Yin WU Yao HU Qi-Gang ZHOU Dan-Lian WU Li-Juan ZHU Department of Pharmacology School of Pharmacy Nanjing Medical University Nanjing 210029 China Department of Pharmacology School of Pharmacy Laboratory of Cerebrovascular Disease Nanjing Medical University Nanjing 210029 China Department of Pharmacology School of Pharmacy Nanjing Maternal and Child Health Hospital Nanjing Medical University Nanjing 210029 China Laboratory of Cerebrovascular Disease Nanjing Medical University Nanjing 210029 China

Objection Epidemiological studies of anxiety disorders have indicated that as many as 29% of people will, at some point in their lives, suffer from anxiety *** serotonergic system is essential for regulating affects and moods, and has long been implicated in the pathogenesis of *** activity of serotonergic pathways is critically regulated by plasma membrane serotonin transporter and serotonin *** various 5-HT receptor subtypes, 5-HT1A receptors have been predominantly involved in anxiety-related ***, the mechanism underlying the role of 5-HT1A receptors in these diseases remains *** Here we show that 5-HT1A R-selective agonist 8-OH-DPAT and selective serotonin reuptake inhibitor (SSRI) fluoxetine down-regulated hippocampal neuronal nitric oxide synthase (nNOS) expression, whereas 5-HT1AR-selective antagonist NAN-190 up-regulated hippocampal nNOS *** assessing anxiety-related behaviors using the novelty suppressed feeding, open-field and elevated plus maze tests, we show that mice lacking nNOS gene (KO) or treated with nNOS-selective inhibitor 7-NI (i.p., 30 mg/kg/d for 28 days, or intrahippocampal microinjection, 16.31 μg/1.0 μL) displayed an anxiolytic-like phenotype, implicating nNOS *** also show that, in wild-type (WT) mice, adminstrations of 8-OH-DPAT (i.p., 0.1 mg/kg/d) or fluoxetine (i.p., 10 mg/kg/d) for 28 days caused anxiolytic-like effects, whereas NAN-190 (i.p., 0.3 mg/kg/d for 28 days) caused anxiogenic-like *** KO mice however, these drugs were ***, intrahippocampal infusion of 8-OH-DPAT (45.963 μg/100 μL) using 14-day osmotic minipump produced anxiolytic *** microinjection of 7-NI (16.31 μg/1.0 μL) abolished the anxiogenic-like effects of intrahippocampal NAN-190 (4.74 μg/1.0 μL).Additionally, NAN-190 decreased and 8-OH-DPAT increased phosphorylated CREB levels in WT mice but not in KO *** of hippocampal CREB phosphorylation

关键词： neuronal nitric oxide synthase 5-HT,5-HT1A-receptor anxiety-related behavior CREB hippocampus

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The neuroprotection of limb ischemic preconditioning in global cerebral ischemia rats and its neuroglobin mechanism

The neuroprotection of limb ischemic preconditioning in glob...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Shu-Qin LI~1,Wen-Bin LI~(1,2,*),Yu-Yan HU~1,Min ZHANG~1,Xiao-Cai SUN~1,Xiao-Hui XIAN~1,Jie QI~1,Qing-Jun LI~1 1 Department of Pathophysiology,Hebei Medical University,Shijiazhuang 050017,China 2 Aging and Cognition Neuroscience Laboratory of Hebei Province,Shijiazhuang 050031,China.

Objective Emerging evidence suggests that limb ischemic preconditioning（LIP） could protect neurons against cerebral ischemia-reperfusion ***,the mechanisms of LIP are not well understood. Neuroglobin（Ngb） is a recently discovered globin that affords protection against hypoxic/ischemic brain *** present study is to investigate the neuroprotection of LIP against global cerebral ischemia and its Ngb mechanism. Methods One hundred and thirty-three male Wistar rats were randomly divided into 7 groups:sham of cerebral ischemia group,cerebral ischemia group,LIP+cerebral ischemia group,AS-ODNs+LIP+cerebral ischemia group, S-ODNs+LIP+cerebral ischemia group,hemin+cerebral ischemia group,and hemin vehicle+cerebral ischemia group. Rats in each group were assigned to 3 observations:（1） mitochondrial Na-K-ATPase activity at 6 h and 24 h,（2） Bcl- 2 and Bax mRNA expression at 24 h,and（3） delayed neuronal death（DND） of pyramidal neurons at 7 d in the CA1 *** Na-K-ATPase activity was measured using *** expression of Bcl- 2 and Bax mRNA were investigated by reverse transcription-polymerase chain reaction（RT-PCR） *** DND of pyramidal neurons in the CA1 hippocampus was evaluated by using thionin staining under light microscope by determining the neuronal density and histological *** Pretreatment with LIP or Ngb inducer hemin before cerebral ischemia preserved mitochondrial Na-K-ATPase activity and offered protection against cerebral ischemia, whereas administration with Ngb antisense oligodeoxynucleotides（AS-ODNs） inhibited the above ***, treatment with LIP or hemin prior to cerebral ischemia dramatically up-regulated Bcl-2 mRNA expression,whereas down-regulated Bax mRNA *** of Ngb AS-ODNs before LIP+cerebral ischemia significantly inhibited Bcl-2 mRNA expression and increased Bax mRNA *** These results indicated that Ngb played an important role in the cereb

关键词： brain ischemia tolerance limb ischemic preconditioning neuroglobin hemin Ngb AS-ODNs hippocampus

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