Neuroendocrine regulation of erythropoiesis following trauma

创伤后红细胞生成的神经内分泌调节

• 批准号: 7625076
• 负责人: ALICIA M MOHR
• 金额: $ 10.26万
• 依托单位: UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-06-01 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7625076
• 关键词: Activation Analysis; Acute; Adenylate Cyclase; Adrenergic Agents; Adrenergic Receptor; Adrenergic beta-Antagonists; Affect; Anemia; Animals; Award; Binding; Biochemical; Bone Marrow; Bone Marrow Cells; Calcium; Catecholamines; Cell Culture Techniques; Cells; Clinical; Complex; Development; Doctor of Philosophy; Effectiveness; Elements; Enzyme-Linked Immunosorbent Assay; Epinephrine; Equilibrium; Erythroid; Erythroid Cells; Erythropoiesis; Erythropoietin; Experimental Models; Faculty; Flow Cytometry; Functional disorder; Goals; Growth; Growth Factor; Hematopoiesis; Hematopoietic; Hematopoietic stem cells; Hemorrhagic Shock; Immunoassay; Inflammatory Response; Injury; Interferon Type II; Laboratories; Measurement; Measures; Mediating; Mediator of activation protein; Medicine; Mentors; Mentorship; Modality; Modeling; Modification; Molecular; Neurosecretory Systems; Norepinephrine; Operative Surgical Procedures; Pancytopenia; Pathway interactions; Plasma; Play; Postdoctoral Fellow; Principal Investigator; Process; Rattus; Regulation; Research Personnel; Resources; Reverse Transcriptase Polymerase Chain Reaction; Rodent; Rodent Model; Role; Shock; Signal Transduction; Staging; Stem cells; Stress; Surgical Models; Sympathetic Nervous System; Techniques; Testing; Therapeutic; Training; Training Programs; Transforming Growth Factor beta; Trauma; Work; adrenergic; base; beta-adrenergic receptor; biological adaptation to stress; career; cell type; cellular development; cytokine; erythroid differentiation; graduate student; member; monolayer; neuroimmunology; novel; professor; progenitor; programs; radioligand; receptor; receptor density; research study; response; response to injury; skills

DESCRIPTION (provided by applicant): This proposal describes a five year training program for the further development of an academic career in Surgery. The principal investigator is currently a faculty member and plans to enhance her scientific skills through an unique integration of interdepartmental resources. The long term goal of this program will evaluate the effects of the neuroendocrine system on erythropoiesis following severe injury. Pranela Rameshwar, PhD will mentor the principal investigator's scientific development. Dr. Rameshwar is a recognized leader in the field of hematopoiesis, stem cells and neuroimmunology. She is an Associate Professor of Medicine and recipient of the Master Educator Award for the training of postdoctoral fellows and graduate students. To enhance this training, this program will also enlist the expertise and mentorship of David H. Livingston, MD, Professor of Surgery. Dr. Livingston has pioneered the study of bone marrow (BM) failure following trauma. Recent work in Dr. Livingston's laboratory has demonstrated that erythropoietic dysfunction occurs following trauma. Acute injury activates the neuroendocrine system and the sympathetic nervous system plays a central role in mediating the counter-regulatory stress response to injury. Sympathetic stimulation accompanies both clinical and experimental trauma as well as hemorrhagic shock and it is known to modulate erythropoiesis under non-stressed conditions. Successful erythropoiesis requires interactions between hematopoietic progenitor cells, BM stroma and the BM microenvironment. The proposed experiments will test the hypothesis that early and persistent adrenergic stimulation of BM after trauma impacts the growth of erythroid cells and contributes to the development of anemia. The specific aims include: 1) Defining alterations in erythropoiesis following modification of adrenergic stimulation, 2) Elucidating the effects of neuroendocrine manipulation on erythroid development and the cellular signaling mechanisms involved, 3) Defining the neuroendocrine effects on BM stroma and BM cytokines. In a rodent model of trauma/hemorrhagic shock with the use of both pharmacologic and surgical models of sympathetic alteration, erythropoiesis will be analyzed utilizing cellular, biochemical and molecular techniques. This proposal is novel and understanding the neuroendocrine mechanism of erythropoiesis following trauma is a preliminary step towards potential therapeutic modalities for the treatment of anemia.

描述(由申请人提供)：本建议书描述了一项五年培训计划，旨在进一步发展外科的学术生涯。首席研究员目前是一名教员，并计划通过独特的跨部门资源整合来提高她的科学技能。该计划的长期目标将评估神经内分泌系统对严重创伤后红细胞生成的影响。Pranela Rameshwar博士将指导首席研究员的科学发展。Rameshwar博士是造血、干细胞和神经免疫学领域公认的领导者。她是医学副教授，并因培养博士后研究员和研究生而获得硕士教育家奖。为了加强这一培训，该计划还将征集医学博士、外科教授戴维·H·利文斯顿的专业知识和指导。利文斯顿博士是创伤后骨髓衰竭研究的先驱。利文斯顿博士的实验室最近的研究表明，创伤后会发生红细胞生成功能障碍。急性损伤激活神经内分泌系统，交感神经系统在介导对损伤的逆调节应激反应中起着中心作用。交感神经刺激伴随着临床和实验创伤以及失血性休克，众所周知，在非应激条件下，交感神经刺激可以调节红细胞生成。成功的红细胞生成需要造血祖细胞、骨髓基质和骨髓微环境之间的相互作用。拟议的实验将检验这样一个假设，即创伤后早期和持续的骨髓肾上腺素能刺激会影响红细胞的生长，并有助于贫血的发展。其具体目的包括：1)明确肾上腺素能刺激修饰后红细胞生成的变化；2)阐明神经内分泌调控对红系发育的影响及其细胞信号机制；3)明确神经内分泌对骨髓基质和骨髓细胞因子的影响。在创伤/失血性休克的啮齿动物模型中，使用交感神经改变的药理学和外科模型，将利用细胞、生化和分子技术分析红细胞生成。这一建议是新颖的，了解创伤后红细胞生成的神经内分泌机制是朝着治疗贫血的潜在治疗方式迈出的第一步。