Overcoming neurogenic “meta-inflammation” to promote recovery after spinal cord injury
克服神经源性“元炎症”以促进脊髓损伤后的恢复
基本信息
- 批准号:9924658
- 负责人:
- 金额:$ 109.71万
- 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:2019-05-01 至 2027-04-30
- 项目状态:未结题
- 来源:
- 关键词:Adipose tissueAdrenal GlandsAffectAnxietyAtherosclerosisBrainBrain DiseasesBrain regionCellsCoupledDataDefectDevelopmentDiseaseDysautonomiasFailureFatigueFundingGoalsGrantHomeostasisHumanImmuneImmune System DiseasesImpaired wound healingImpairmentIndividualInfectionInflammationInjuryLifeLiverLungMetabolicMetabolismMicroscopicMuscleNational Institute of Neurological Disorders and StrokeNeuroimmuneNon-Insulin-Dependent Diabetes MellitusOrganPathologicPathologyQuality of lifeRecoveryRecovery of FunctionReflex controlResearchSkinSpinalSpinal cord injurySpinal cord injury patientsSpleenSurvival RateSystemTestingUnited States National Institutes of HealthWalkingautonomic reflexbody systemchronic depressioncomorbiditydesignexperimental studyimprovedinjury and repairnon-alcoholic fatty liver diseasenovelprogramsrestorationstandard of caresuccesstool
项目摘要
The singular goal of most spinal cord injury (SCI) research programs is to repair the injured spinal cord and restore locomotor
function. Unfortunately, restoration of walking is a low priority for most SCI individuals 1. In addition to impaired mobility, SCI
causes slow and steady pathological changes in organ systems throughout the body. Failure to recognize and treat multi-
organ system pathology as a standard of care may explain why survival rates have not improved for SCI patients (relative to
able-bodied individuals) over the past 30 years 2. Emerging data indicate that after SCI, the loss of sympathetic tone and the
development of aberrant spinal autonomic reflexes that control immune organs (e.g., spleen) and the major organs that control
metabolism (e.g., liver, adrenal gland, muscle, adipose tissue and gut) cause immune dysfunction and multi-organ pathology.
Thus, mitigating the onset and downstream consequences of post-injury dysautonomia could improve immune and metabolic
homeostasis. Since immune and metabolic processes are normally tightly coupled and are essential for life 3,4, it is likely that
most, if not all, co-morbidities that affect SCI individuals (e.g., spontaneous infections in lung or skin, impaired wound healing,
non-alcoholic fatty liver disease (NAFLD), chronic depression, atherosclerosis, type 2 diabetes, fatigue and anxiety), can be
explained by impaired immunometabolism. Experiments in this proposal are designed to study SCI as a disease of the entire
body and will test the overall hypothesis that post-injury dysautonomia breaks neuro-immune homeostasis creating a state of
“neurogenic meta-inflammation”. This proposal is an integration of currently funded NINDS R01 grants and new ideas. All
experiments and concepts will build on my lab's past successes using both “macroscopic” (systems and networks) and
“microscopic” (cells to molecules) tools to study the pathophysiological significance of neuro-immune interactions. Just as
recent NIH initiatives have emphasized that cures for human brain disease are likely to arise from better understanding of
brain networks or circuits, rather than defects in a single brain region, a cure for SCI is unlikely to originate from a focus only
on repairing the injured spinal cord.
大多数脊髓损伤 (SCI) 研究项目的唯一目标是修复受伤的脊髓并恢复运动能力
功能。不幸的是,对于大多数 SCI 患者来说,恢复行走并不是优先考虑的事情 1。除了活动能力受损之外,SCI
导致全身器官系统缓慢而稳定的病理变化。未能识别和治疗多发性
器官系统病理学作为护理标准可以解释为什么 SCI 患者的生存率没有提高(相对于
2. 新出现的数据表明,脊髓损伤后,交感神经张力的丧失和
控制免疫器官(例如脾脏)和控制的主要器官的异常脊髓自主反射的发展
新陈代谢(例如肝脏、肾上腺、肌肉、脂肪组织和肠道)会导致免疫功能障碍和多器官病理。
因此,减轻损伤后自主神经功能障碍的发作和下游后果可以改善免疫和代谢
体内平衡。由于免疫和代谢过程通常紧密耦合并且对生命至关重要 3,4,因此很可能
大多数(如果不是全部)影响 SCI 个体的合并症(例如,肺部或皮肤自发感染、伤口愈合受损、
非酒精性脂肪性肝病 (NAFLD)、慢性抑郁症、动脉粥样硬化、2 型糖尿病、疲劳和焦虑)
解释为免疫代谢受损。本提案中的实验旨在研究 SCI 作为一种全身性疾病。
身体并将测试总体假设,即受伤后自主神经失调会破坏神经免疫稳态,从而产生一种状态
“神经源性元炎症”。该提案整合了当前资助的 NINDS R01 赠款和新想法。全部
实验和概念将建立在我的实验室过去使用“宏观”(系统和网络)和
研究神经免疫相互作用的病理生理学意义的“微观”(细胞到分子)工具。正如
美国国立卫生研究院 (NIH) 最近的举措强调,人类大脑疾病的治疗方法可能来自于更好地了解
大脑网络或回路,而不是单个大脑区域的缺陷,SCI 的治疗不太可能仅源于焦点
关于修复受伤的脊髓。
项目成果
期刊论文数量(0)
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会议论文数量(0)
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PHILLIP G POPOVICH其他文献
PHILLIP G POPOVICH的其他文献
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{{ truncateString('PHILLIP G POPOVICH', 18)}}的其他基金
Overcoming Neurogenic “Meta-Inflammation” to Promote Recovery After Spinal Cord Injury
克服神经源性“元炎症”以促进脊髓损伤后的恢复
- 批准号:
10634510 - 财政年份:2019
- 资助金额:
$ 109.71万 - 项目类别:
Eighteenth International Symposium on Neural Regeneration (ISNR)
第十八届国际神经再生研讨会(ISNR)
- 批准号:
9913669 - 财政年份:2019
- 资助金额:
$ 109.71万 - 项目类别:
Overcoming Neurogenic “Meta-Inflammation” to Promote Recovery After Spinal Cord Injury
克服神经源性“元炎症”以促进脊髓损伤后的恢复
- 批准号:
10400875 - 财政年份:2019
- 资助金额:
$ 109.71万 - 项目类别:
Overcoming Neurogenic “Meta-Inflammation” to Promote Recovery After Spinal Cord Injury
克服神经源性“元炎症”以促进脊髓损伤后的恢复
- 批准号:
10160976 - 财政年份:2019
- 资助金额:
$ 109.71万 - 项目类别:
Role of the spinal cord - gut - immune axis after spinal cord injury
脊髓损伤后脊髓-肠道-免疫轴的作用
- 批准号:
9380128 - 财政年份:2017
- 资助金额:
$ 109.71万 - 项目类别:
Glucocorticoids and sensory neuron plasticity
糖皮质激素和感觉神经元可塑性
- 批准号:
9381698 - 财政年份:2017
- 资助金额:
$ 109.71万 - 项目类别:
Preventing autonomic dysreflexia to restore immune function after SCI
预防 SCI 后自主神经反射异常以恢复免疫功能
- 批准号:
8812278 - 财政年份:2014
- 资助金额:
$ 109.71万 - 项目类别:
TREM2 regulation of macrophages in spinal cord injury and CNS endogenous repair
TREM2对脊髓损伤和中枢神经系统内源性修复中巨噬细胞的调节
- 批准号:
8024876 - 财政年份:2011
- 资助金额:
$ 109.71万 - 项目类别:
TREM2 regulation of macrophages in spinal cord injury and CNS endogenous repair
TREM2对脊髓损伤和中枢神经系统内源性修复中巨噬细胞的调节
- 批准号:
8311626 - 财政年份:2011
- 资助金额:
$ 109.71万 - 项目类别:
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