HMGB1 and Traumatic Brain Injury
HMGB1 和创伤性脑损伤
基本信息
- 批准号:8525465
- 负责人:
- 金额:$ 30.41万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2009
- 资助国家:美国
- 起止时间:2009-09-01 至 2015-08-31
- 项目状态:已结题
- 来源:
- 关键词:AcuteAcute Brain InjuriesAddressAmericanAstrocytesBiological MarkersBrainBrain EdemaCause of DeathCerebral EdemaCerebral IschemiaCerebrospinal FluidClinicalClinical ManagementComaCraniocerebral TraumaDataDevelopmentEconomic BurdenEdemaEtiologyEventExtracellular SpaceFutureGeneticGlutamate ReceptorGlutamatesGoalsHMGB ProteinsHMGB1 ProteinHumanIncidenceIndividualInflammationInflammatoryInterleukin-1 ReceptorsIntracranial HypertensionKnockout MiceLaboratoriesLesionLigandsLiquid substanceMeasurementMeasuresMediatingMedicalMembrane ProteinsMilitary PersonnelMolecularMusMutant Strains MiceN-Methyl-D-Aspartate ReceptorsNMDA receptor A1Natural ImmunityNecrosisNervous System TraumaNeurological outcomeNeuronal InjuryNeuronsOutcomePathway interactionsPatientsProcessRodentRoleScanningSecondary toSensorimotor functionsSerumSignal TransductionSocietiesSwellingTherapeuticTimeToll-like receptorsTraumatic Brain InjuryWorkX-Ray Computed Tomographyaquaporin 4basecell typecellular developmentclinically relevantdisabilityexcitotoxicityextracellularimprovedinhibitor/antagonistinsightmortalityneuroinflammationnew therapeutic targetnovelnovel therapeuticsoutcome forecastreceptortoll-like receptor 4transcription factorwater channelyoung adult
项目摘要
Project Summary
Traumatic brain injury (TBI) is a devastating neurological injury afflicting over 1
million people annually, including a large number of young adults and military
personnel. Cerebral edema is associated with increased intracranial pressure
(ICP) and a poor clinical outcome following TBI, although the cellular
mechanisms underlying this process remain unknown. This gap in the
understanding of cerebral edema formation contributes to the lack of clinically-
effective therapeutics for TBI patients. Recent work by our laboratory
demonstrates that acute neuronal necrosis stimulates the passive release of high
mobility group box protein 1 (HMGB1), which in turn induces glial swelling and
cerebral edema. Specific Aim 1 will establish whether activation of individual
NMDA receptor subunits increase neuronal injury and cerebral edema following
experimental TBI. The incorporation of NR2A and NR2B knockout mice will
determine whether individual NR2 subunits contribute to HMGB1 release, brain
swelling, and neurological outcome using following head trauma. Specific Aim
2 will determine whether toll-like receptor-4 (TLR4) mediates the pro-
inflammatory and cerebral edema promoting effects of HMGB1. The ability of
HMGB1 to stimulate the astrocytic water channel, AQP4, will also be addressed
in TLR4 mutant mice. Specific Aim 3 will determine whether HMGB1 may
represent a novel biomarker to predict the development of cerebral edema
folowing head trauma in humans. Measurement of HMGB1 levels within the
cerebrospinal fluid (CSF) and serum of neurotrauma patients will be correlated
with acute neuronal injury and neurological outcome. Together, the proposed
studies will investigate the novel possibility that HMGB1-TLR4 signaling
contributes to the development of cerebral edema and increased ICP following
TBI. The results of these studies may support the future development of novel
therapeutics directed against this pathway to limit neurological injury following
head trauma.
项目摘要
创伤性脑损伤(TBI)是一种毁灭性的神经损伤,
每年有100万人,其中包括大量的年轻人和军人。
人员的脑水肿与颅内压增高有关
(ICP)和TBI后的不良临床结果,尽管细胞
这一过程的基本机制仍不清楚。的这一缺陷
对脑水肿形成的理解有助于缺乏临床-
对TBI患者的有效治疗。我们实验室最近的工作
表明急性神经元坏死刺激高浓度的
迁移率族蛋白1(HMGB 1),这反过来又诱导神经胶质肿胀,
脑水肿具体目标1将确定是否激活个人
NMDA受体亚单位增加神经元损伤和脑水肿
实验性脑外伤NR 2A和NR 2B基因敲除小鼠的掺入将使NR 2A和NR 2B基因敲除小鼠的免疫应答增加。
确定单个NR 2亚基是否有助于HMGB 1的释放,
肿胀和神经学结果。具体目标
2将确定Toll样受体-4(TLR 4)是否介导促凋亡,
HMGB 1的炎症和脑水肿促进作用。的能力
HMGB 1刺激星形胶质细胞水通道,AQP 4,也将得到解决
在TLR 4突变小鼠中。具体目标3将确定HMGB 1是否可能
代表了一种新的生物标志物来预测脑水肿的发展
人类头部创伤后死亡HMGB 1水平的测量
脑外伤患者的脑脊液(CSF)和血清将相关
伴有急性神经元损伤和神经学结果。在一起,拟议的
研究将探讨HMGB 1-TLR 4信号转导的新可能性,
导致脑水肿的发展和颅内压升高,
创伤性脑损伤这些研究结果可能会支持未来的发展小说
针对该途径的治疗以限制以下神经损伤:
头部外伤
项目成果
期刊论文数量(19)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Attenuation of hematoma size and neurological injury with curcumin following intracerebral hemorrhage in mice.
- DOI:10.3171/2011.2.jns10784
- 发表时间:2011-07
- 期刊:
- 影响因子:4.1
- 作者:King MD;McCracken DJ;Wade FM;Meiler SE;Alleyne CH Jr;Dhandapani KM
- 通讯作者:Dhandapani KM
Curcumin attenuates cerebral edema following traumatic brain injury in mice: a possible role for aquaporin-4?
- DOI:10.1111/j.1471-4159.2010.06630.x
- 发表时间:2010-05
- 期刊:
- 影响因子:4.7
- 作者:Laird MD;Sukumari-Ramesh S;Swift AE;Meiler SE;Vender JR;Dhandapani KM
- 通讯作者:Dhandapani KM
High mobility group box protein-1 promotes cerebral edema after traumatic brain injury via activation of toll-like receptor 4.
- DOI:10.1002/glia.22581
- 发表时间:2014-01
- 期刊:
- 影响因子:6.2
- 作者:Laird MD;Shields JS;Sukumari-Ramesh S;Kimbler DE;Fessler RD;Shakir B;Youssef P;Yanasak N;Vender JR;Dhandapani KM
- 通讯作者:Dhandapani KM
Necrostatin-1 reduces neurovascular injury after intracerebral hemorrhage.
- DOI:10.1155/2014/495817
- 发表时间:2014
- 期刊:
- 影响因子:0
- 作者:King MD;Whitaker-Lea WA;Campbell JM;Alleyne CH Jr;Dhandapani KM
- 通讯作者:Dhandapani KM
Remote ischemic post-conditioning promotes hematoma resolution via AMPK-dependent immune regulation.
- DOI:10.1084/jem.20171905
- 发表时间:2018-10-01
- 期刊:
- 影响因子:0
- 作者:Vaibhav K;Braun M;Khan MB;Fatima S;Saad N;Shankar A;Khan ZT;Harris RBS;Yang Q;Huo Y;Arbab AS;Giri S;Alleyne CH Jr;Vender JR;Hess DC;Baban B;Hoda MN;Dhandapani KM
- 通讯作者:Dhandapani KM
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KRISHNAN M. DHANDAPANI其他文献
KRISHNAN M. DHANDAPANI的其他文献
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{{ truncateString('KRISHNAN M. DHANDAPANI', 18)}}的其他基金
Immunometabolic regulation after CNS injury
中枢神经系统损伤后的免疫代谢调节
- 批准号:
10737334 - 财政年份:2023
- 资助金额:
$ 30.41万 - 项目类别:
Remote ischemic Conditioning Promotes Cerebrovascular Recovery after Intracerebral Hemorrhage
远程缺血调理促进脑出血后脑血管恢复
- 批准号:
10676330 - 财政年份:2020
- 资助金额:
$ 30.41万 - 项目类别:
Remote ischemic Conditioning Promotes Cerebrovascular Recovery after Intracerebral Hemorrhage
远程缺血调理促进脑出血后脑血管恢复
- 批准号:
10240740 - 财政年份:2020
- 资助金额:
$ 30.41万 - 项目类别:
Remote ischemic Conditioning Promotes Cerebrovascular Recovery after Intracerebral Hemorrhage
远程缺血调理促进脑出血后脑血管恢复
- 批准号:
10459588 - 财政年份:2020
- 资助金额:
$ 30.41万 - 项目类别:
Remote ischemic Conditioning Promotes Cerebrovascular Recovery after Intracerebral Hemorrhage
远程缺血调理促进脑出血后脑血管恢复
- 批准号:
10035049 - 财政年份:2020
- 资助金额:
$ 30.41万 - 项目类别:
Therapeutic targeting of CD36 after intracerebral hemorrhage
脑出血后 CD36 的治疗靶向
- 批准号:
8432013 - 财政年份:2012
- 资助金额:
$ 30.41万 - 项目类别:
Therapeutic targeting of CD36 after intracerebral hemorrhage
脑出血后 CD36 的治疗靶向
- 批准号:
8303510 - 财政年份:2012
- 资助金额:
$ 30.41万 - 项目类别: