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Recombinant Human Erythropoietin Augments Neovascularization Responses in a Neonatal Rat Model of Premature Brain Damage by Phosphatidylinositol 3 Kinase/Akt Pathway

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Chinese Medical Journal 2017年第7期130卷 854-858页

作者： Da-Fan Yu Li-Hua Zhu Li Jiang Department of Clinical Medcine Medical School of Southeast University Jiangsu 210009 China 2Department of Pediatrics Zhongda Hospital Southeast University Nanjing Jiangsu 210009 China

Background：Recombinant human-erythropoietin （rh-EPO） has therapeutic efficacy for premature infants with brain damage during the active rehabilitation and *** the present study,we found that the rh-EPO was related to the promotion *** aim was to investigate whether rh-EPO augments neovascularization in the neonatal rat model of premature brain damage through the phosphatidylinositol 3 kinase （PI3K）/protein kinase B （Akt） signaling ***：Postnatal day 5 （PD5）,rats underwent permanent ligation of the right common carotid artery and were exposed to hypoxia for 2 *** the rat pups were randomized into five groups as follows：（1） control group;（2） hypoxia-ischemic （HI） group;（3） HI ＋ LY294002 group;（4） HI ＋ rh-EPO group;and （5） HI ＋ rh-EPO ＋ LY294002 *** phospho-Akt protein was tested 90 min after the whole operation,and CD34,vascular endothelial growth factor receptor 2 （VEGFR2）,and vascular endothelial growth factor （VEGF） were also tested 2 days after the whole ***：In the hypoxic and ischemic zone of the premature rat brain,the rh-EPO induced CD34＋ cells to immigrate to the HI brain zone （P 〈 0.05） and also upregulated the VEGFR2 protein expression （P 〈 0.05） and VEGF mRNA level （P 〈 0.05） through the PI3K/Akt （P 〈 0.05） signaling pathway when compared with other ***：The rh-EPO treatment augments neovascularization responses in the neonatal rat model of premature brain damage through the PI3K/Akt signaling ***,the endogenous EPO may exist in the HI zone of rat brain and also has neovascularization function through the PI3K/Akt signaling pathway.

关键词： Erythropoietin hypoxia-ischemia Neovascularization Premature Brain

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Correlation between aquaporin-4 and brain edema in an animal model of astrocytic oxygen-glucose deprivation and reintroduction

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Neural Regeneration Research 2010年第9期5卷 695-699页

作者： Yimin Hua Yi Qu Li Zhang Long Xiang Department of Pediatrics West China Second University Hospital Sichuan University Chengdu 610041 Sichuan Province China Department of Pediatrics Pediatric Research Institute of Beijing Military Region Beijing 100700 China

BACKGROUND：Previous studies have demonstrated that aquaporin-4 （AQP4） plays a key role in the formation and resolution of brain ***,the molecular mechanisms and role of AQP4 in hypoxia-ischemia-induced brain edema remain poorly ***：To establish a newborn animal model of astrocytic oxygen-glucose deprivation and reintroduction,to observe the correlation between AQP4 and cellular volume,and to investigate the role of AQP4 in the development of brain edema following oxygen deprivation and ***,TIME AND SETTING：A comparative experiment was performed at the Experimental Center of West China Second University Hospital between October 2007 and April ***：Astrocytes were derived from the neocortex of Sprague Dawley rats aged 3 ***：Astrocytes were incubated in glucose/serum-free Dulbecco＇s modified Eagle＇s medium,followed by 1% oxygen for 6 ***,oxygen-glucose deprivation and reintroduction models were successfully *** OUTCOME MEASURES：Real-time polymerase chain reaction and Western blot analysis were used to measure expression of AQP4 mRNA and protein in cultured rat astrocytes following oxygen-glucose deprivation and *** cellular volume,as determined by [3H]-3-O-methyl-D-glucose,was used to represent the extent of astrocytic ***：During oxygen-glucose deprivation,AQP4 mRNA and protein expression gradually decreased in astrocytes,whereas cellular volume increased in a time-dependent manner （P〈 0.01）.Following oxygen-glucose reintroduction,AQP4 mRNAand protein expression was upregulated,peaked at day 7,and then gradually decreased,but still higher than normal levels （P 〈 0.05）.However,cellular volume gradually decreased （P 〈 0.01）,and then reached normal levels at day ***：AQP4 expression highly correlated with cellular volume changes,suggesting that AQP4 played an important role in modulating brain water transport in an astrocytic oxygen-glucose dep

关键词： aquaporin-4 astrocytes edema hypoxia-ischemia glucose reintroduction brain injury neural regeneration

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Can we further optimize therapeutic hypothermia for hypoxic-ischemic encephalopathy?

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Neural Regeneration Research 2019年第10期14卷 1678-1683页

作者： Anthony Davies Guido Wassink Laura Bennet Alistair J.Gunn Joanne O.Davidson Department of Physiology The University of Auckland

Perinatal hypoxic-ischemic encephalopathy is a leading cause of neonatal death and *** hypothermia significantly reduces death and major disability associated with hypoxic-ischemic encephalopathy;however,many infants still experience lifelong disabilities to movement,sensation and *** guidelines,based on strong clinical and preclinical evidence,recommend therapeutic hypothermia should be started within 6 hours of birth and continued for a period of 72 hours,with a target brain temperature of 33.5 ±0.5℃ for infants with moderate to severe hypoxic-ischemic *** clinical guidelines also recommend that infants be re warmed at a rate of 0.5℃ per hour,but this is not based on strong *** are no randomized controlled trials investigating the optimal rate of rewarming after therapeutic hypothermia for infants with hypoxic-ischemic *** studies of rewarming are conflicting and results were confounded by treatment with sub-optimal durations of *** this review,we evaluate the evidence for the optimal start time,duration and depth of hypothermia,and whether the rate of rewarming after treatment affects brain injury and neurological outcomes.

关键词： hypoxia-ischemia hypoxic-ischemic encephalopathy therapeutic hypothermia neuroprotection therapeutic strategies randomized controlled trials animal models fetal sheep piglets

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Acupuncture preconditioning protects hippocampal neurons from transient ischemia/reperfusion injury

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Neural Regeneration Research 2011年第15期6卷 1175-1179页

作者： Mingshan Wang Haipeng Zhou Fei Shi Shilong Ma Yanlin Bi Yuqiu Liu Hong Liu Haiou Li Department of Anesthesiology Qingdao Eastern Municipal Hospital Qingdao 266071 Shandong Province China Department of Anesthesiology Qingdao Bone Injury Hospital Qingdao 266021 Shandong Province China Department of Anesthesiology Jining First People's Hospital Jining 272111 Shandong Province China

The present study established a model of brain ischemia in aged rats using four-vessel *** observed hippocampal CA1 neuronal apoptosis and apoptosis-mediated protease caspase-3 expression following preconditioning of electroacupuncture at Baihui（GV 20）.Our results showed that the number of hippocampal CA1 normal neurons was decreased,and degenerated neurons were increased 12 hours to 3 days following cerebral ischemia/*** number of hippocampal CA1 apoptotic neurons and caspase-3-positive neurons in rats with cerebral ischemia/reperfusion injury was significantly decreased following acupuncture *** preconditioning protects aged rats against ischemia/reperfusion injury by regulating caspase-3 protein expression.

关键词： acupuncture preconditioning hypoxia-ischemia brain aging apoptosis neural regeneration

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Role of apoptosis-inducing factor in perinatal hypoxic-ischemic brain injury

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Neural Regeneration Research 2021年第2期16卷 205-213页

作者： Juan Rodriguez Tao Li Yiran Xu Yanyan Sun Changlian Zhu Center for Brain Repair and Rehabilitation Institute of Neuroscience and PhysiologySahlgrenska AcademyUniversity of GothenburgGothenburgSweden Henan Key Laboratory of Child Brain Injury Institute of Neuroscience and Third Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina Department of Anatomy School of Basic Medical ScienceZhengzhou UniversityZhengzhouHenan ProvinceChina Department of Women’s and Children’s Health Karolinska InstitutetStockholmSweden

Perinatal complications,such as asphyxia,can cause brain injuries that are often associated with subsequent neurological deficits,such as cerebral palsy or mental *** mechanisms of perinatal brain injury are not fully understood,but mitochondria play a prominent role not only due to their central function in metabolism but also because many proteins with apoptosis-related functions are located in the *** these proteins,apoptosis-inducing factor has already been shown to be an important factor involved in neuronal cell death upon hypoxia-ischemia,but a better understanding of the mechanisms behind these processes is required for the development of more effective treatments during the early stages of perinatal brain *** this review,we focus on the molecular mechanisms of hypoxic-ischemic encephalopathy,specifically on the importance of apoptosis-inducing *** relevance of apoptosis-inducing factor is based not only because it participates in the caspase-independent apoptotic pathway but also because it plays a crucial role in mitochondrial energetic functionality,especially with regard to the maintenance of electron transport during oxidative phosphorylation and in oxidative stress,acting as a free radical *** also discuss all the different apoptosis-inducing factor isoforms discovered,focusing especially on apoptosis-inducing factor 2,which is only expressed in the brain and the functions of which are starting now to be ***,we summarized the interaction of apoptosis-inducing factor with several proteins that are crucial for both apoptosis-inducing factor functions(prosurvival and pro-apoptotic)and that are highly important in order to develop promising therapeutic targets for improving outcomes after perinatal brain injury.

关键词： apoptosis apoptosis inducing factor asphyxia cell death free radical hypoxia-ischemia mitochondria neonates oxidative stress

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The regulatory effect of memantine on expression and synthesis of heat shock protein 70 gene in neonatal rat models with cerebral hypoxic ischemia

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Chinese Medical Journal 2003年第4期116卷 558-564页

作者：陈惠金刘志伟周泽汉蒋明华钱龙华吴圣楣 Xinhua Hospital Shanghai Second Medical University Department of Biomedical Engineering Shanghai Second Medical University

To evaluate the neuroprotective effect of memantine, a non-competitive antagonist at the N-methyl-D-aspartate receptor, against hypoxic ischemia (HI) by exploring its regulation on the expression and synthesis of heat shock protein 70 (HSP70) gene in neonatal rat models with cerebral HI Methods Memantine was intraperitoneally injected at a dose of 20 mg/kg in neonatal rat models either before (PRE group) or after (POST group) induction of HI The expression and synthesis of the HSP70 gene and its corresponding product were determined by rapid competitive PCR and immunohistochemistry, respectively Results There was an increase in the expression of HSP70 mRNA two hours after induction of HI, which reached its peak at 48 hours, then decreased gradually The same expression occurred at relatively low levels in the control group Also, HSP70 synthesis was detected as early as 2h after HI, reached its peak between 48 and 72 hours, then declined over time After memantine administration, the expression of the gene and its synthesis of the corresponding product decreased significantly during the time intervals 24-72 h for the gene and 48-72 h for the product compared to the HI group Conclusion It was shown that HI is very sensitive to the expression of the HSP70 gene and synthesis of its corresponding product, which could be regulated by memantine The latter may have the ability to reduce brain damage; thus decreased HSP70 mRNA expression could be a marker for HI It is suggested that memantine can be a promising agent for neuroprotection against HI, although an overall and abstract assessment of memantine is required to see if it can be used on neonates clinically later on

关键词： memantine heat shock protein 70 gene brain hypoxia-ischemia neonatal rat

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Therapeutic effect of placenta-derived mesenchymal stem cells on hypoxic-ischemic brain damage in rats

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World Journal of Pediatrics 2015年第1期11卷 74-82页

作者： Hong-Fang Ding Hui Zhang Hui-Fang Ding Dong Li Xin-Hao Yi Xin-Yi Gao Wei-Wei Mou Xiu-Li Ju Department of Pediatrics Qilu HospitalShandong UniversityJinan 250012China Department of Pediatrics Shengli Oil Field Central HospitalDongying 257034China Department of Neurology Qingdao Municipal HospitalQingdao 266000China

Background:Oxidative stress is involved in the development of hypoxic-ischemic brain damage(HIBD).In this study,we investigated the therapeutic efcts of placenta-derived mesenchymal stem cells(PD-MSCs)and explored the N F-E2-related factor-2/heme oxygenase-1(Nrf2/HO-1)signaling pathway in treating ***:P7 rats were subjected to hypoxic-ischemic brain injury and randomly divided into four groups(control,HIBD,HIBD+PD-MSCs,and HIBD+fbroblasts).Forty-eight hours after the induction of HIBD,5×10^(5)of PD-MSCs were injected into cerebral tissue in the HIBD+PD-MSCs group,while the same dose of fibroblas ts were injected in the HIBD+fibroblasts *** Water Maze,gross and pathological changes were tested at *** level of malondialdehyde(MDA)was detected in rats'***-PCR and western blot analysis were used to evaluate the changes of Nrf2/***:The HIBD group showed significantly longer escape latency and a lower frequency of original platform crossing in the Morris Water M laze compared with the control *** receiving PD MSCs showed significant improvement of *** pathological changes were evident after HIBD,but ameliorated in the PD-MSCs *** with the control group,HO-1 and Nrf2 were up-regulated at gene and protein levels in the HI brain,beginning at 6 hours and peaking at 48 hours(P<0.05).The expression of HO-1 and Nrf2 in the PD-MSCs treatment group was more pronounced than in the HBD group(P<0.01).PD MSCs also decreased MDA production in the brain ***:These results demonstrate that PD-MSCs have neuroprotective effect during the treatment of HIBD and that the mechanism may be partly due to alleviating oxidative stress.

关键词： hypoxia-ischemia mesenchymal stem cells neonatal rat oxidative stress

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Expression of neuroglobin in ocular hypertension induced acute hypoxic-ischemic retinal injury in rats

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International Journal of Ophthalmology(English edition) 2011年第4期4卷 393-395页

作者： Shao-Yang Shi Xue-Mei Feng You Li Xun Li and Xiao-Long Chen Department of Ophthalmology Shengjing Hospital of China Medical University Shenyang 11004 Liaoning Province China

AIM: To investigate the Expression of neuroglobin (Ngb) in the retina of rats with ocular hypertension induced acute retinal hypoxic-ischemic injury. METHODS: Seventy Wistar rats were divided into 7 groups randomly. The Experimental model was induced by elevation of intraocular pressure via anterior chamber canula insertion in the left eyes and the fellow eyes were preserved as normal controls. The retinal tissues were taken at 1, 5, 10, 15, 20, 30 and 60 minutes after hypoxic-ischemia injury. Protein was extracted, and then analyzed by Western-blot method. SPSS was used for statistical analysis. RESULTS: The time-depended expressions of Ngb were observed. The level of Ngb increased rapidly at 1 minute after ischemia and reached to the peak at 5 minutes, which had significant difference from that of control group (P 0.05). CONCLUSION: The expression of Ngb in retinal tissue increased rapidly after hypoxic-ischemic injury in rats, suggesting that Ngb may play an important role in the process of acute retinal hypoxic-ischemic injury.

关键词： hypoxia-ischemia neuroglobin retina

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Supplementary of unsaturated fatty acids during perinatal periods obviously relieve the brain injury and behavioral deficits in neonatal hypoxiaischemia

Supplementary of unsaturated fatty acids during perinatal pe...

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中国神经科学学会第四次会员代表大会暨第七届全国学术会议

作者： Wen-Ting ZHANG,Hui GAO,Yan-Qin GAO State key laboratory of Medical Neurobiology,Shanghai Medicine College,Fudan University,Shanghai 200032

＜正＞Objective Perinatal hypoxia-ischemia is an important cause of brain injury in newborns,with a high risk of future behavioral and neurological *** is also the major cause of neurological diseases such as dementia,epilepsy and *** apoptosis play an important role in perinatal ***,people use olive oil for cooking and/or get extra fish oil daily for health,in order to prevent against the stroke and cardiovascular *** fish oil and olive oil are found in significant amount of unsaturated fatty acids（UFA）,which including Monounsaturated fatty acid（mainlyα-linoleic acid） and polyunsaturated fatty acids（for exampleα-linolenic acid,Eicosapentaenic acid and Docosahexaenic acid）.They are essential components of the biomembrane and play an important role in the most of physiological process in brain like excitable membrane function,memory and *** the present study,our purpose is to determine whether supplementation offish oil and olive oil could protect neurons from apoptosis in hypoxiaischemia *** Supplementing the fish oil and olive oil to normal diets（1 g oil /20 g diet）,and these special diets were given to the rats during the rats were pregnant and up to 7 d after neonatal hypoxia-ischemia（HI）.Neonatal hypoxiaischemia operation was done in 7-old d *** brain injury volume were performed at 7 d and 8 laser-doppler flowmetry laser-doppler flowmetry weeks after *** neurological Outcome,using the righting reflex,gait reflex,negative geotaxis, grid walking and footfault test,were assessed up to 50 d after *** data are expressed as mean±SD,and statistic analysis was performed using ANOVA and post hoc Fisher’s PLSD tests,with P＜0.05 considered statistically *** Supplementary of both olive oil and fish oil to pregnant rats significantly reduce the brain injury volume in neonatal hypoxia-ischemia（the percentage of brain injury volume of regular diet group is（42.9±6.3）%,while

关键词： unsaturated fatty acids fish oil olive oil hypoxia-ischemia neuroprotection

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缺血缺氧后新生大鼠海马NR1-mRNA表达的变化及羟丁酸钠对其的影响

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国际麻醉学与复苏杂志 2006年第3期27卷 134-136,154页

作者：马正良曾因明张研于常州南京大学医学院附属鼓楼医院麻醉科 210008 江苏省麻醉医学研究所江苏省麻醉学重点实验室徐州市221002

Objective To investigate the effect of sodium hydroxybutyrate(GHB) on expression of hippocampal N-methyl-D-aspartate receptor 1 subunit (NR1) mRNA in the neonatal rat with hypoxic-ischemic insult. Methods One hundred eighty seven-day(7d) old Sprague Dawley rat pups of either sex weighting 10 g～14 g were randomly assigned to sham group(S), normal saline group(C),GHB 50 mg/kg group(γ50),GHB 100 mg/kg group(γ100)and GHB 200 mg/kg group(γ200),n=*** procedure for the induction of hypoxia-ischemia was done according to the way described by Rice:under ether anesthesia,pups were subjected to left carotid artery ligated followed by 2 h of hypoxic exposure(O2:N2=8﹪:92﹪).The pups in S group were only aparted left carotid artery which was not obturated and no *** 50 mg/kg, 100 mg/kg, 200 mg/kg was administered i.p immediately after hypoxia,then a time every 8h inγ50、γ100 and γ200 group *** same volume normal saline was administered i.p in the same way in S and C *** transcriptase polymerase chain reaction(RT-PCR) was used to analyze the expression of NR1 mRNA semi-quantificationally in the left hippocampus at 2 h、6 h、12 h、1 d、3 d、7 d after insult in S、C、γ50、γ100 and γ200 group. Results The difference of expression of NR1 mRNA between S and C group wasn’t *** any time after insult, The differences of expression of NR1 mRNA among C and three GHB group were not significant too. Conclusion hypoxia-ischemia and GHB didn’t significantly affect the expression of NR1 mRNA in neonatal rat hippocampus.

关键词： neonatal rat hippocampus hypoxia-ischemia n-methyl-D-aspartate sodium hydroxybutyrate

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