GENE EXPRESSION IN BRAIN INJURY

脑损伤中的基因表达

• 批准号: 6243407
• 负责人: FRANK WELSH
• 金额: $ 17.32万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-08-01 至 1998-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6243407
• 关键词: brain injury; calbindin; cerebral ischemia /hypoxia; chemoprevention; decarboxylases; electrophysiology; enkephalins; gamma aminobutyrate; gene expression; genetic regulation; heme; immunocytochemistry; in situ hybridization; laboratory rat; microtubule associated protein; neural transmission; neurofilament; neurogenetics; neurotrophic factors; oxygenases; potassium chloride; protooncogene; spreading cortical depression; stress proteins; trauma

Trauma to the Central Nervous System (CNS) initiates a cascade of physiologic and molecular events that culminate in cellular injury and damage. Recent studies indicate that cells respond to trauma and other insults by altering the expression of specific genes. Among the genes expressed following CNS trauma are the immediate early genes (IEGs), many of which encode transcription factors. A second group of genes induced by CNS injury are those encoding heat-shock proteins (HSPs). Although the expression of these genes may be involved in the attempted recovery of function following brain trauma, little is known about the identity of the genes induced by trauma or the temporal/anatomic relationship between this induction and traumatic injury. Moreover, the consequences of post-traumatic induction of IEGs and HSPs remains poorly defined. This study will use molecular biology techniques to identify key changes in gene expression following experimental brain injury and relate these changes to histologic injury. Using in situ hybridization and immunohistochemistry, we will determine the timecourse and regional expression of several IEGs (c-fos, c-jun, junB, zif-268) in several models of brain trauma. We will then determine whether trauma-induced expression of IEGs is followed by expression of critical target genes, including proenkephalin, brain-derived neurotropic factor (BDNF), calbindin-D28K, and microtubule-associated protein (MAP2). We will also determine the timecourse and regional expression of hsp72, hsp90, and hsp32 (heme-oxygenase) following brain injury. Finally, we will correlate changes in gene expression with indicators of cell injury, including cellular calcium staining, blood-brain-barrier function, histologic damage and immunocytochemistry for glutamic acid decarboxylase (GAD). These studies will enhance our understanding of the cellular and molecular events following trauma and may lead to the development of novel targeted therapies for the treatment of traumatic brain injury.

中枢神经系统（CNS）的创伤引发了一系列的 导致细胞损伤的生理和分子事件， 损害 最近的研究表明，细胞对创伤和其他 通过改变特定基因的表达来进行攻击。 的基因中 在CNS创伤后表达的是立即早期基因（IEG），许多 它们编码转录因子。 第二组基因诱导 由CNS损伤引起的是编码热休克蛋白（HSP）的那些。 虽然 这些基因的表达可能与试图恢复 脑外伤后的功能，很少有人知道的身份， 由创伤或颞/解剖关系诱导的基因 和外伤之间的联系 此外，后果 创伤后IEG和HSP的诱导仍然不清楚。 这项研究将使用分子生物学技术来确定关键的变化 在实验性脑损伤后基因表达中以及与这些基因表达相关的 组织学损伤的变化。 用原位杂交和 免疫组化，我们将确定时间进程和区域 在几种细胞中表达几种IEGs（c-fos，c-jun，junB，zif-268）， 脑外伤的模型 然后我们将确定是否由创伤引起的 IEG的表达之后是关键靶基因的表达， 包括脑啡肽原、脑源性神经营养因子（BDNF）， calbindin-D28 K和微管相关蛋白（MAP 2）。 我们还将 确定热休克蛋白72、热休克蛋白90和 hsp 32（血红素加氧酶）。 最后我们将 将基因表达的变化与细胞损伤的指标相关联， 包括细胞钙染色，血脑屏障功能， 谷氨酸脱羧酶组织损伤及免疫细胞化学研究 （GAD）。 这些研究将增强我们对细胞和 创伤后的分子事件，并可能导致 用于治疗创伤性脑损伤的新型靶向疗法。