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
基本信息
- 批准号:10676330
- 负责人:
- 金额:$ 38.09万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-09-01 至 2025-07-31
- 项目状态:未结题
- 来源:
- 关键词:5&apos-AMP-activated protein kinaseAcuteAffectAgeAmericanAnti-Inflammatory AgentsArchitectureArteriesBlood PressureBlood VesselsBlood capillariesBone MarrowBrainBrain InjuriesBrain hemorrhageCellsCerebral Amyloid AngiopathyCerebral IschemiaCerebral hemisphere hemorrhageCerebral small vessel diseaseCerebrovascular CirculationChronicClinicalClinical TrialsDevelopmentDrug KineticsEndotheliumEssential Fatty AcidsExcisionExerciseExhibitsExtracellular Matrix ProteinsFDA approvedFatty AcidsGoalsHematomaHumanHypertensionImmuneInflammationInterventionIntracranial Arterial StenosisIschemiaIschemic StrokeLimb structureMacrophageMediatingMediatorMedical AssistanceMetabolicMusMyelogenousMyeloid Cell ActivationMyocardial InfarctionNervous System PhysiologyNeurologicNeurological outcomeNeuroprotective AgentsNutrientOutcomePathway interactionsPatientsPhase I Clinical TrialsPre-Clinical ModelPredispositionProductionProteinsQuality of lifeRecoveryRegulationResearchResolutionRuptureSafetyStrokeSubarachnoid HemorrhageSurvivorsTestingTherapeuticTissuesVascular DementiaVascular remodelingVascularizationangiogenesisarmarterioleblood vessel developmentcerebrovascularclinical translationcomorbiditycost effectivedietarydisabilityendothelial stem cellimprovedinjuredinnovationischemic conditioninglimb ischemiamortalityneovascularizationneural networkneurogenesisneurological recoveryneurorestorationpreservationrepairedresponserestorationsexstem cellstargeted treatmenttissue repairtranslational studywhite matter injury
项目摘要
PROJECT SUMMARY
Intracerebral hemorrhage (ICH), the most common form of hemorrhagic stroke, accounts for up to 15% of all
strokes. ICH, which affects 67,000 Americans annually, induces the highest acute mortality and the worst long-
term neurological outcomes of all types of stroke. Primary ICH is caused by the rupture of small vessels damaged
by chronic hypertension or cerebral amyloid angiopathy. The resultant hematoma disrupts neural networks and
damages the vascular architecture, culminating in a loss of brain function and the need for lifelong medical
assistance. Re-establishment of a functional cerebrovascular network of small arteries and arterioles is a
prerequisite for the removal of damaged tissue and for restoration of cerebral blood flow to deliver nutrients,
trophic factors, and stem cells within the injured brain. Thus, there is a dire need for neurorestorative therapies
that provide cerebrovascular recovery after ICH. Remote ischemic conditioning (RIC), the repetitive delivery of
sub-lethal ischemia to a remote limb, demonstrated safety, versatility, and efficacy in early stage clinical trials;
however, the utility of RIC after ICH remains understudied. The objective of this proposal is to test the
overarching hypothesis that RIC induces vascular remodeling and improves long-term neurological function
via anti-inflammatory myeloid cell activation after ICH. Specific Aim 1 will test the hypothesis that myeloid
AMPKα1 mediates RIC-induced vascular repair after ICH. Specific Aim 2 will test the hypothesis that RIC
increases angiogenesis via Del-1 release after ICH. Specific Aim 3 will test the hypothesis that delayed
implementation of RIC improves chronic ICH outcomes in a sex- and age-independent manner. Expected
outcomes of the proposed research include the identification of RIC as a clinically-safe, non-invasive
intervention to promote cerebrovascular recovery after ICH. As ICH patients exhibit high permanent disability
rates that diminish quality of life, our proposed research will identify a simple therapy to harness an endogenous
pathway of neurological repair, providing an innovative and cost-effective approach to rehabilitate chronic ICH
patients.
.
项目总结
脑出血(ICH)是出血性中风最常见的形式,占所有中风的15%
中风。每年影响6.7万美国人的ICH,导致最高的急性死亡率和最严重的长期-
所有类型中风的长期神经学结局。原发性脑出血是由损伤的小血管破裂引起的
由慢性高血压或脑淀粉样血管病引起。由此产生的血肿扰乱了神经网络,
破坏血管结构,最终导致大脑功能丧失,需要终身医疗
援助。重建由小动脉和小动脉组成的功能性脑血管网络是一种
移除受损组织和恢复脑血流以提供营养的先决条件,
营养因子和受损脑组织中的干细胞。因此,迫切需要神经恢复性疗法。
为脑出血后脑血管的恢复提供帮助。远程缺血适应(RIC),重复传递
远端肢体的亚致死性缺血,在早期临床试验中证明了安全性、多功能性和有效性;
然而,ICH后RIC的应用仍未得到充分的研究。这项提案的目标是测试
RIC诱导血管重塑和改善长期神经功能的重要假说
通过脑出血后抗炎髓系细胞的激活。特殊目标1将检验髓系细胞
AMPKα1介导RIC诱导的脑出血后血管修复具体目标2将检验大米的假设
脑出血后通过释放Del-1促进血管生成。《特定目标3》将检验这一假设
RIC的实施以性别和年龄无关的方式改善慢性脑出血的预后。预期
拟议的研究结果包括将RIC确定为临床安全的、非侵入性的
促进脑出血后脑血管恢复的干预措施。由于脑出血患者表现出高度永久性残疾
降低生活质量的比率,我们提议的研究将确定一种简单的治疗方法来驾驭内源性
神经修复途径,为慢性脑出血的康复提供了一种创新和经济有效的方法
病人。
。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
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 }}
KRISHNAN M. DHANDAPANI其他文献
KRISHNAN M. DHANDAPANI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('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:
$ 38.09万 - 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:
$ 38.09万 - 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:
$ 38.09万 - 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:
$ 38.09万 - 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:
$ 38.09万 - 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:
$ 38.09万 - 项目类别:
相似海外基金
Pharmacological targeting of AMP-activated protein kinase for immune cell regulation in Type 1 Diabetes
AMP 激活蛋白激酶对 1 型糖尿病免疫细胞调节的药理学靶向
- 批准号:
2867610 - 财政年份:2023
- 资助金额:
$ 38.09万 - 项目类别:
Studentship
Establishing AMP-activated protein kinase as a regulator of adipose stem cell plasticity and function in health and disease
建立 AMP 激活蛋白激酶作为脂肪干细胞可塑性和健康和疾病功能的调节剂
- 批准号:
BB/W009633/1 - 财政年份:2022
- 资助金额:
$ 38.09万 - 项目类别:
Fellowship
Determining the role of AMP-activated protein kinase in the integration of skeletal muscle metabolism and circadian biology
确定 AMP 激活蛋白激酶在骨骼肌代谢和昼夜节律生物学整合中的作用
- 批准号:
532989-2019 - 财政年份:2021
- 资助金额:
$ 38.09万 - 项目类别:
Postdoctoral Fellowships
Metabolic control of integrin membrane traffic by AMP-activated protein kinase controls cell migration.
AMP 激活的蛋白激酶对整合素膜运输的代谢控制控制着细胞迁移。
- 批准号:
459043 - 财政年份:2021
- 资助金额:
$ 38.09万 - 项目类别:
Studentship Programs
Determining the role of AMP-activated protein kinase in the integration of skeletal muscle metabolism and circadian biology
确定 AMP 激活蛋白激酶在骨骼肌代谢和昼夜节律生物学整合中的作用
- 批准号:
532989-2019 - 财政年份:2020
- 资助金额:
$ 38.09万 - 项目类别:
Postdoctoral Fellowships
The Role of AMP-activated Protein Kinase in GVHD-causing T Cells
AMP 激活的蛋白激酶在引起 GVHD 的 T 细胞中的作用
- 批准号:
10561642 - 财政年份:2019
- 资助金额:
$ 38.09万 - 项目类别:
Determining the role of AMP-activated protein kinase in the integration of skeletal muscle metabolism and circadian biology
确定 AMP 激活蛋白激酶在骨骼肌代谢和昼夜节律生物学整合中的作用
- 批准号:
532989-2019 - 财政年份:2019
- 资助金额:
$ 38.09万 - 项目类别:
Postdoctoral Fellowships
Treating Diabetic Inflammation using AMP-Activated Protein Kinase Activators
使用 AMP 激活的蛋白激酶激活剂治疗糖尿病炎症
- 批准号:
2243045 - 财政年份:2019
- 资助金额:
$ 38.09万 - 项目类别:
Studentship
The Role of AMP-activated Protein Kinase in GVHD-causing T Cells
AMP 激活的蛋白激酶在引起 GVHD 的 T 细胞中的作用
- 批准号:
10359032 - 财政年份:2019
- 资助金额:
$ 38.09万 - 项目类别:
Investigating the therapeutic potential of AMP-activated protein kinase in myotonic dystrophy type 1
研究 AMP 激活蛋白激酶在 1 型强直性肌营养不良中的治疗潜力
- 批准号:
428988 - 财政年份:2019
- 资助金额:
$ 38.09万 - 项目类别:
Studentship Programs