The Structural and Molecular Basis of Blast-Induced Vascular Injury
爆炸引起的血管损伤的结构和分子基础
基本信息
- 批准号:10455436
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-04-01 至 2023-03-31
- 项目状态:已结题
- 来源:
- 关键词:AcuteAffectAfghanistanAlzheimer&aposs disease modelAreaAstrocytesBasement membraneBehaviorBehavioralBiochemical MarkersBiotinBlast InjuriesBlood - brain barrier anatomyBlood VesselsBrain InjuriesCerebrovascular systemCerebrumChronicChronic PhaseCognitiveComplementComputer softwareConflict (Psychology)DataDextransElectron MicroscopyEvolutionGlial Fibrillary Acidic ProteinHistologicHourImmunohistochemistryInjuryIntermediate Filament ProteinsIraqLabelLengthMass Spectrum AnalysisMental HealthModelingMolecularMorbidity - disease rateNerveNeurofilament-HNeuronsPathologyPericytesPost-Traumatic Stress DisordersPreparationProcessPropertyProteinsProteomicsRattusResearchResearch PersonnelRoleScanningSmooth MuscleSurfaceTechniquesTestingTimeTraumatic Brain InjuryVeteransWestern Blottingantagonistaquaporin 4attenuationbehavior testbehavioral phenotypingblast exposuredensityimprovedmetabotropic glutamate receptor 2microCTmild traumatic brain injurymilitary servicemortalitymouse modelneurofilamentneurovascularneurovascular unitnovelnovel therapeutic interventionreceptorstress related disordertraittreatment strategyvascular injury
项目摘要
Traumatic brain injury (TBI) has been a major cause of mortality and morbidity in the recent
conflicts in Iraq and Afghanistan. Much concern exists over the role of TBI in the chronic
cognitive and behavioral effects that can develop during or after military service. Most injuries in
the recent conflicts have been mild TBIs (mTBIs) due to blast exposure. Vascular damage is
well established as a significant component of blast injury. Indeed under the conditions of
exposure in the model under study at the histological level the cerebral vasculature seems to be
selectively vulnerable. Using micro computed tomography (CT) scanning we found that blast
induces widespread attenuation of the brain vasculature. In proteomic studies on isolated
microvascular preparations obtained two months following injury one of the most highly altered
proteins identified by mass spec (MS) was found to be glial fibrillary acidic protein (GFAP),
which was decreased by blast-exposure. This finding was confirmed by Western blotting on
isolated microvascular preps. The loss of GFAP seemed to suggest that following blast injury
astrocytic endfeet were becoming detached from cerebral vessels and immunostaining of
isolated microvascular preps supported this speculation. Interestingly of the first 9 proteins
identified by MS several others were neuronal intermediate filament proteins including the
neurofilament heavy chain (NF-H) and α- internexin, which like GFAP, were decreased following
blast injury. Loss of these proteins suggests that nerve terminals become detached from
cerebral vessels as well. Disrupted gliovascular and neurovascular connections could affect a
number of cerebral functions. The proposed studies will determine the chronic structural and
functional consequences of blast injury on the vasculature in a rat model of low-level blast
exposure. The studies will utilize quantitative immunohistochemistry, stereology, electron
microscopy, Western blotting of isolated microvascular preps, micro CT scanning and behavior.
We will test the hypothesis that blast injury causes widespread loss of gliovascular and
neurovascular connections and determine the functional consequences. We will also determine
whether a treatment that improves the post-traumatic stress disorder (PTSD)-related behavioral
traits that develop in this model stimulates gliovascular and neurovascular connections as well
improves the vascular pathology observed on micro CT scanning. Three-time points post-
blast exposure will be examined (48 hours, 6 weeks and 8 months) to capture the evolution of
the injury from acute into subacute and chronic phases.
创伤性脑损伤(TBI)已成为近年来死亡和发病的主要原因
人们对伊拉克和阿富汗冲突中的慢性创伤性脑损伤的作用深感担忧。
大多数损伤可能发生在服兵役期间或之后。
最近的冲突是由于爆炸暴露导致的轻度创伤性脑损伤 (mTBI)。
事实上,在以下条件下,它已被确定为爆炸损伤的一个重要组成部分。
在组织学水平上研究的模型中,脑血管系统的暴露似乎是
通过显微计算机断层扫描(CT)扫描,我们发现了爆炸。
在分离的蛋白质组学研究中引起脑血管系统的广泛衰减。
受伤后两个月获得的微血管制剂是变化最大的之一
通过质谱(MS)鉴定的蛋白质被发现是胶质纤维酸性蛋白(GFAP),
免疫印迹证实了这一发现。
孤立的微血管制剂的 GFAP 损失似乎表明爆炸损伤后。
星形细胞末足与脑血管分离,免疫染色
分离的微血管制剂支持了前 9 种蛋白质的这一推测。
通过 MS 鉴定出其他几种是神经中间丝蛋白,包括
神经丝重链 (NF-H) 和 α-internexin 与 GFAP 一样,在以下情况下减少
这些蛋白质的丢失表明神经末梢脱落。
脑血管和神经血管连接中断也会影响。
拟议的研究将确定慢性结构和大脑功能的数量。
低水平爆炸大鼠模型中爆炸损伤对脉管系统的功能影响
这些研究将利用定量免疫组织化学、体视学、电子学。
显微镜检查、分离微血管制备物的蛋白质印迹、显微 CT 扫描和行为。
我们将检验爆炸损伤导致胶质血管和神经胶质细胞广泛损失的假设。
我们还将确定神经血管连接并确定功能后果。
是否有一种治疗可以改善创伤后应激障碍(PTSD)相关行为
该模型中发展的特征也会刺激胶质血管和神经血管连接
改善显微 CT 扫描后三个时间点观察到的血管病理学。
将检查爆炸暴露情况(48 小时、6 周和 8 个月),以捕捉
损伤由急性期进入亚急性期和慢性期。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Gregory A. Elder其他文献
Identification and neuron specific expression of the S182/presenilin I protein in human and rodent brains
人类和啮齿动物大脑中 S182/早老素 I 蛋白的鉴定和神经元特异性表达
- DOI:
- 发表时间:
1996 - 期刊:
- 影响因子:0
- 作者:
Gregory A. Elder;N. Tezapsidis;J. Carter;J. Shioi;C. Bouras;H;J. M. Johnston;S. Efthimiopoulos;V. Friedrich;N. Robakis - 通讯作者:
N. Robakis
Apathy in Lewy body disease and its effects on functional impairment over time
路易体病的冷漠及其对功能障碍随时间的影响
- DOI:
10.3389/fneur.2024.1339190 - 发表时间:
2024-01-18 - 期刊:
- 影响因子:3.4
- 作者:
Carolyn W. Zhu;H. Grossman;Gregory A. Elder;Howie J Rosen;Mary Sano - 通讯作者:
Mary Sano
Gregory A. Elder的其他文献
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{{ truncateString('Gregory A. Elder', 18)}}的其他基金
The role of metabotropic mGluR2 receptors in the chronic cognitive and behavioral effects of blast exposure
代谢型 mGluR2 受体在爆炸暴露的慢性认知和行为影响中的作用
- 批准号:
10693237 - 财政年份:2022
- 资助金额:
-- - 项目类别:
The role of metabotropic mGluR2 receptors in the chronic cognitive and behavioral effects of blast exposure
代谢型 mGluR2 受体在爆炸暴露的慢性认知和行为影响中的作用
- 批准号:
10538740 - 财政年份:2022
- 资助金额:
-- - 项目类别:
ShEEP Request for Zeiss Modular Laser Scanning Microscope LSM 980
ShEEP 请求蔡司模块化激光扫描显微镜 LSM 980
- 批准号:
10175791 - 财政年份:2020
- 资助金额:
-- - 项目类别:
The Structural and Molecular Basis of Blast-Induced Vascular Injury
爆炸引起的血管损伤的结构和分子基础
- 批准号:
10158420 - 财政年份:2019
- 资助金额:
-- - 项目类别:
Neurodegeneration following low-level blast exposure
低水平爆炸暴露后的神经变性
- 批准号:
10269000 - 财政年份:2018
- 资助金额:
-- - 项目类别:
Neurodegeneration following low-level blast exposure
低水平爆炸暴露后的神经变性
- 批准号:
10066266 - 财政年份:2018
- 资助金额:
-- - 项目类别:
The Neurobiology of Blast-Related Brain Injury in a Rat Model of mTBI
mTBI 大鼠模型中爆炸相关脑损伤的神经生物学
- 批准号:
8676382 - 财政年份:2014
- 资助金额:
-- - 项目类别:
The Neurobiology of Blast-Related Brain Injury in a Rat Model of mTBI
mTBI 大鼠模型中爆炸相关脑损伤的神经生物学
- 批准号:
9261394 - 财政年份:2014
- 资助金额:
-- - 项目类别:
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