Oxidative stress in regional cerebral blood flow alterations after cardiac arrest
心脏骤停后局部脑血流变化的氧化应激
基本信息
- 批准号:8321601
- 负责人:
- 金额:$ 12.59万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2008
- 资助国家:美国
- 起止时间:2008-09-01 至 2014-02-28
- 项目状态:已结题
- 来源:
- 关键词:3-nitrotyrosineAccident and Emergency departmentAcuteAdvisory CommitteesAlbuminsAreaAscorbic AcidAsphyxiaAutoradiographyAwardBehavioralBiologyBlood VesselsBrainBrain regionC14 isotopeCerebrovascular CirculationCerebrumChildChildhoodChromatographyClinicalDeoxyglucoseDependencyDevelopmentElectron Spin Resonance SpectroscopyEmergency MedicineEmergency SituationEnzyme-Linked Immunosorbent AssayEquilibriumFellowshipFluorescenceGlucoseGrantGuidelinesHeart ArrestHigh Pressure Liquid ChromatographyHippocampus (Brain)Hydrogen PeroxideHyperemiaImmunofluorescence ImmunologicImmunohistochemistryImpairmentInterventionK-Series Research Career ProgramsKnowledgeLiquid substanceMagnetic Resonance ImagingMeasurementMeasuresMedicineMemoryMentorsMetabolicMetabolismMorbidity - disease rateMotorNeurologicNitratesNitric OxideNitrogenOutcomeOutcome AssessmentOxidative StressOxygenPediatric HospitalsPhasePhysiciansPlayProductionProtocols documentationPublic HealthRattusReactive Nitrogen SpeciesReactive Oxygen SpeciesReduced GlutathioneResearchResearch PersonnelResearch TrainingResuscitationRoleScientistSpin LabelsStaining methodStainsStressSurvivorsTestingThalamic structureThickTissuesTrainingUnited StatesUnited States National Institutes of HealthWeightWorkcareer developmentdidactic educationdisabilityfluoro jadeimprovedin vivomorris water mazemortalitymultidisciplinaryneuronal survivalneuropathologynitrosative stressoutcome forecastpostnatalpreventprogramssensorsuccesstherapeutic target
项目摘要
DESCRIPTION (provided by applicant): Pediatric cardiac arrest remains a significant cause of mortality and morbidity and thus it is an important public health problem. In the United States, it is estimated that 16,000 children die annually of cardiac arrest. Asphyxia is the cause of cardiac arrest in the majority of pediatric victims. Most survivors have severe neurological impairment. Cerebral blood flow (CBF) disturbances after resuscitation may further contribute to neuropathological damage after cardiac arrest. Reactive oxygen and nitrogen species play an important role in regulating CBF, and are generated during and after resuscitation from cardiac arrest. CBF, cerebral metabolism, oxidative stress, nitrative stress and the interaction of these factors remain to be defined in pediatric cardiac arrest, and may represent an important therapeutic target toward improving outcome of this debilitating condition. The candidate recently has developed a protocol for serial and regional assessment of CBF in developing postnatal day 17 rats via arterial spin label MRI and found insult duration dependency of CBF after asphyxial cardiac arrest. The candidate will (i) determine the relationship between CBF, cerebral metabolism and neuropathological damage and (ii) quantify production of nitric oxide, reactive oxygen species and other reactive nitrogen species after two durations of asphyxial cardiac arrest (8.5 min and 12 min). The candidate will also (iii) determine if scavenging ROS and RNS in either vascular or parenchyma! compartments will prevent pathological CBF alterations and reduce neuropathological damage after asphyxial cardiac arrest. Regional CBF will be measured serially via arterial spin label MRI. Cerebral metabolic rate for glucose will be measured with autoradiography. Nitric oxide will be measured in vivo serially with tissue minisensors and ex vivo with electron paramagnetic resonance spectroscopy. Oxidative and nitrosative stress will also be quantified: we will measure 3-nitrotyrosine by ELISA and immunofluorescence, ascorbic acid by high liquid field chromatography, and reduced glutathione by fluorescence. The candidate is a pediatric emergency physician at Children's Hospital of Pittsburgh. There is a need for training pediatric emergency clinician-scientists, as interventions likely to impact outcome after pediatric cardiac arrest should ideally be started at the arrest scene or in the Emergency Department. This Mentored Career Development Award will allow the candidate to pursue a unique and highly integrated mentored program in resuscitation medicine. To assure success in becoming an independent clinician-scientist, the candidate assembled a multidisciplinary and multi-institutional advisory committee that includes senior mentors with special expertise in 1) resuscitation research, 2) vascular biology, 3) oxidative stress, 4) MRI and 5) pediatric clinical resuscitation guidelines development and implementation.
描述(申请人提供):儿科心脏骤停仍然是死亡率和发病率的一个重要原因,因此是一个重要的公共卫生问题。在美国,据估计,每年有16,000名儿童死于心脏骤停。窒息是大多数儿科患者心脏骤停的原因。大多数幸存者都有严重的神经损伤。复苏后的脑血流(CBF)障碍可能进一步导致心脏骤停后的神经病理损害。活性氧和氮在调节CBF中起着重要作用,它们是在心脏骤停复苏期间和复苏后产生的。在儿童心脏骤停中,脑血流、脑代谢、氧化应激、硝化应激以及这些因素的相互作用仍有待确定,并可能代表改善这一衰弱疾病预后的重要治疗目标。这位候选人最近开发了一套通过动脉自旋标记磁共振成像对出生后第17天发育的大鼠进行CBF连续和区域性评估的方案,并发现了窒息心脏骤停后CBF的损伤持续时间相关性。候选人将(I)确定CBF、脑代谢和神经病理损害之间的关系,以及(Ii)量化窒息心脏骤停两个持续时间(8.5分钟和12分钟)后一氧化氮、活性氧和其他活性氮的产生。候选人还将(Iii)确定是否清除血管或实质中的ROS和RNS!间隔区将防止窒息心脏骤停后的病理性CBF改变,减少神经病理损害。局部脑血流量将通过动脉自旋标记磁共振连续测量。大脑对葡萄糖的代谢率将用放射自显影进行测量。一氧化氮将用组织微型传感器在体内连续测量,并在体外用电子顺磁共振波谱进行测量。氧化和亚硝化应激也将被量化:我们将用ELISA法和免疫荧光法测定3-硝基酪氨酸,用高液相色谱法测定抗坏血酸,用荧光法测定还原型谷胱甘肽。候选人是匹兹堡儿童医院的儿科急诊医生。有必要对儿科急诊临床医生-科学家进行培训,因为在儿科心脏骤停后,可能影响预后的干预措施最好从急诊现场或急诊科开始。这项导师职业发展奖将允许候选人在复苏医学领域追求独特的、高度整合的导师计划。为了确保成功地成为一名独立的临床科学家,候选人组建了一个多学科和多机构的咨询委员会,其中包括具有1)复苏研究、2)血管生物学、3)氧化应激、4)核磁共振和5)儿科临床复苏指南制定和实施方面专门知识的高级导师。
项目成果
期刊论文数量(4)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Current and future therapies of pediatric cardiopulmonary arrest.
小儿心肺骤停的当前和未来治疗。
- DOI:10.1007/s12098-008-0117-3
- 发表时间:2008
- 期刊:
- 影响因子:4.3
- 作者:Manole,MioaraD;Hickey,RobertW;Clark,RobertSB;Kochanek,PatrickM
- 通讯作者:Kochanek,PatrickM
Pediatric basic and advanced life support: 2010 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations.
- DOI:10.1542/peds.2010-2972a
- 发表时间:2010-11
- 期刊:
- 影响因子:8
- 作者:Kleinman ME;de Caen AR;Chameides L;Atkins DL;Berg RA;Berg MD;Bhanji F;Biarent D;Bingham R;Coovadia AH;Hazinski MF;Hickey RW;Nadkarni VM;Reis AG;Rodriguez-Nunez A;Tibballs J;Zaritsky AL;Zideman D;Pediatric Basic and Advanced Life Support Chapter Collaborators
- 通讯作者:Pediatric Basic and Advanced Life Support Chapter Collaborators
"Lost in translation?" Noninvasive cerebral monitoring after cardiac arrest.
“迷失在翻译中?”
- DOI:10.1097/ccm.0b013e31822b3863
- 发表时间:2011
- 期刊:
- 影响因子:8.8
- 作者:Manole,MioaraD;Kochanek,PatrickM;Clark,RobertS
- 通讯作者:Clark,RobertS
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Mioara D. Manole其他文献
Success of Pediatric Intubations Performed by a Critical Care Transport Service
重症监护转运服务成功实施儿科插管
- DOI:
- 发表时间:
2019 - 期刊:
- 影响因子:2.4
- 作者:
S. Ramgopal;Sean E Button;Sylvia Owusu;Mioara D. Manole;R. Saladino;F. Guyette;C. Martin - 通讯作者:
C. Martin
Rodent Model of Pediatric Asphyxial Cardiac Arrest
小儿窒息心脏骤停啮齿动物模型
- DOI:
- 发表时间:
2019 - 期刊:
- 影响因子:0
- 作者:
Mioara D. Manole;R. Hickey;H. Alexander;R. Clark - 通讯作者:
R. Clark
Cardiac Arrest Secondary to Lightning Strike
雷击继发的心脏骤停
- DOI:
- 发表时间:
2017 - 期刊:
- 影响因子:1.4
- 作者:
Elena L Rotariu;Mioara D. Manole - 通讯作者:
Mioara D. Manole
Cerebral Hypoperfusion and Other Shared Brain Pathologies in Ischemic Stroke and Alzheimer’s Disease
- DOI:
doi: 10.1007/s12975-017-0570-2 - 发表时间:
2017 - 期刊:
- 影响因子:
- 作者:
Shuying Dong;Shelly Maniar;Mioara D. Manole;Dandan Sun - 通讯作者:
Dandan Sun
Strengthening the link between pre-clinical and clinical resuscitation research.
加强临床前和临床复苏研究之间的联系。
- DOI:
- 发表时间:
2020 - 期刊:
- 影响因子:6.5
- 作者:
P. Kochanek;Mioara D. Manole;C. Callaway - 通讯作者:
C. Callaway
Mioara D. Manole的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Mioara D. Manole', 18)}}的其他基金
Targeting vascular contractile cells in capillary stasis after cardiac arrest
心脏骤停后毛细血管停滞中靶向血管收缩细胞
- 批准号:
10194732 - 财政年份:2021
- 资助金额:
$ 12.59万 - 项目类别:
Targeting vascular contractile cells in capillary stasis after cardiac arrest
心脏骤停后毛细血管停滞中靶向血管收缩细胞
- 批准号:
10376256 - 财政年份:2021
- 资助金额:
$ 12.59万 - 项目类别:
CYP 450-mediated CBF Dysregulation and Neurotoxicity in Pediatric Cardiac Arrest
CYP 450 介导的小儿心脏骤停中的 CBF 失调和神经毒性
- 批准号:
9282359 - 财政年份:2013
- 资助金额:
$ 12.59万 - 项目类别:
CYP 450-mediated CBF Dysregulation and Neurotoxicity in Pediatric Cardiac Arrest
CYP 450 介导的小儿心脏骤停中的 CBF 失调和神经毒性
- 批准号:
8594361 - 财政年份:2013
- 资助金额:
$ 12.59万 - 项目类别:
CYP 450-mediated CBF Dysregulation and Neurotoxicity in Pediatric Cardiac Arrest
CYP 450 介导的小儿心脏骤停中的 CBF 失调和神经毒性
- 批准号:
8862518 - 财政年份:2013
- 资助金额:
$ 12.59万 - 项目类别:
Oxidative stress in regional cerebral blood flow alterations after cardiac arrest
心脏骤停后局部脑血流变化的氧化应激
- 批准号:
7510708 - 财政年份:2008
- 资助金额:
$ 12.59万 - 项目类别:
Oxidative stress in regional cerebral blood flow alterations after cardiac arrest
心脏骤停后局部脑血流变化的氧化应激
- 批准号:
7681562 - 财政年份:2008
- 资助金额:
$ 12.59万 - 项目类别:
Oxidative stress in regional cerebral blood flow alterations after cardiac arrest
心脏骤停后局部脑血流变化的氧化应激
- 批准号:
7912903 - 财政年份:2008
- 资助金额:
$ 12.59万 - 项目类别:
Oxidative stress in regional cerebral blood flow alterations after cardiac arrest
心脏骤停后局部脑血流变化的氧化应激
- 批准号:
8136219 - 财政年份:2008
- 资助金额:
$ 12.59万 - 项目类别: