The Effects of Microglia on Oligodendrocyte Cell Death

小胶质细胞对少突胶质细胞死亡的影响

• 批准号: 7495740
• 负责人: BRANDON A MILLER
• 金额: $ 4.55万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-15 至 2009-09-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7495740
• 关键词: Accounting; Actins; Address; Affect; Agonist; Asses; Brain Hypoxia-Ischemia; Cell Communication; Cell Death; Cells; Central Nervous System Diseases; Cessation of life; Coculture Techniques; Condition; Development; Disease; Environment; Experimental Models; Exposure to; Free Radicals; Future; Generations; Glutamate Receptor; Glutamates; Immunohistochemistry; In Vitro; Incubators; Infection; Injury; Kainic Acid; Laboratories; Lipopolysaccharides; Measures; Mediating; Mediator of activation protein; Microglia; Modeling; Neuraxis; Neurotransmitters; Oligodendroglia; Oligonucleotides; Oxygen; Pathway interactions; Physical condensation; Poison; Predisposing Factor; Predisposition; Process; Production; Reporting; Source; Staging; Toxic effect; Trauma; Tumor Necrosis Factor-alpha; cytokine; day; design; extracellular; human disease; insight; research study; response

DESCRIPTION (provided by applicant): Oligodendrocyte (oligo) cell death occurs in response to several pathophysiological processes, including ischemia, hypoxia, infection and trauma. Several laboratories have shown that oligos in the above models of injury die or are damaged by excessive amounts of the neurotransmitter glutamate. However, there are varying reports of just how susceptible oligos are to glutamate, and it is not known what factors are responsible these differing results. The proposed studies will begin to determine how the extracellular environment in a damaged central nervous system (CNS) changes oligos' response to glutamate. This proposal will focus on how two factors - oxygen changes and the presence of microglia - affect oligos vulnerability to toxic substances released during CNS trauma and disease. Using Oligodendrocyte and microglia cultures, both in isolation and combination, along with oxygen-regulating incubators and the glutamate receptor agonist kainic acid, the proposed experiments will help determine what conditions and cellular responses in the CNS mediate oligo death, and provide insights into future therapies to protect oligos in multiple diseases.

描述（由申请人提供）： 少突胶质细胞（Oligo）细胞死亡是针对几种病理生理过程的响应，包括缺血，缺氧，感染和创伤。几个实验室已经表明，上述损伤模型中的寡素死亡或因神经递质谷氨酸的过多而损坏。但是，有各种各样的报道，关于谷氨酸的易感性寡素的方式，尚不知道哪些因素是这些不同结果的原因。拟议的研究将开始确定受损中枢神经系统（CNS）中细胞外环境如何改变寡核酸对谷氨酸的反应。该提案将重点介绍两个因素如何变化和小胶质细胞的存在 - 影响寡核酸对中枢神经系统创伤和疾病期间释放的有毒物质的脆弱性。使用少突胶质细胞和小胶质细胞培养物，无论是孤立和组合的，以及氧调节的孵化器和谷氨酸受体激动剂kainic酸Kainic Acid，拟议的实验将有助于确定CNS中的条件和细胞反应介导了寡核酸酯，并为未来的Therapies提供了多种疾病的洞察力。