Acute astrocyte pathology after traumatic brain injury

超出所提供的空间。 本研究的长期目标是研究创伤性脑损伤后急性星形胶质细胞损伤和死亡的机制，并制定减轻这些损伤机制的治疗策略。我们使用神经解剖学、神经影像学和行为学技术来研究创伤性脑损伤的解剖学和功能性后果，目的是了解病理机制并制定治疗策略。创伤性脑损伤是一个严重的健康问题，在美国每年导致超过230，000人住院治疗和50，000人死亡。TBI的幸存者往往会留下长期残疾。 星形胶质细胞是胶质细胞中数量最多的一种类型，并提供许多重要的功能来支持神经元，包括代谢和营养物质的交换，神经递质的清除以及神经元附近离子浓度的维持。当细胞外谷氨酸和钾离子浓度升高时，星形胶质细胞功能在创伤性脑损伤后可能具有重要意义。 在创伤性脑损伤后数小时内，在随后表现出显著神经元细胞变性和损失的脑区域中发生对星形胶质细胞的严重损伤。我们推测星形胶质细胞的早期损伤部分是由于通过钠依赖性谷氨酸转运蛋白和1型钠质子交换剂的激活进入星形胶质细胞的细胞内钠大量增加。由此产生的细胞内钠增加促进星形胶质细胞钠钙交换器的逆转，产生过量的细胞内钙，最终导致星形胶质细胞死亡。我们将使用已建立的细胞培养损伤模型来测试和完善这些假设。我们将使细胞受到创伤性损伤，并在测量细胞内离子浓度和细胞活力的同时操纵各种钠和钙转运蛋白。这些信息将用于探索针对这些钠和钙损伤机制的新型药理学操作。在这些体内治疗研究中，我们将使用解剖学标记物测量星形胶质细胞和神经元活力，使用磁共振成像测量脑水肿，并使用大鼠创伤性脑损伤后感觉运动功能和学习记忆的行为测量来测量功能结果。性能现场=

EXCEED THE SPACE PROVIDED. The long-term objective of this research is to examine mechanisms of acute astrocyte damage and death following traumatic brain injury and to develop treatment strategies for attenuating these injury mechanisms. We address anatomical and functional consequences of traumatic brain injury using neuroanatomical, neuroimaging, and behavioral techniques with the goal of understanding the pathological mechanism and developing therapeutic strategies. Traumatic brain injury is a significant health problem that results in more than 230,000 hospitalizations and 50,000 deaths per year in the USA. Survivors of TBI are often left with long-term disability. Astrocytes are the most numerous type of gila cells and provide many important functions to support neurons including exchange of metabolic and nutritional material, clearance of neurotransmitters, and maintenance of ion concentrations in the vicinity of neurons. Astrocyte function is likely to have great importance after traumatic brain injury when extracellular glutamate and potassium concentrations are elevated. Severe damage to astrocytes occurs within hours after traumatic brain injury in brain regions that later exhibit significant neuronal cell degeneration and loss. We hypothesize that the early damage to astrocytes is due, in part, to large increases in intracellular sodium that enter astrccytes through sodium-dependent glutamate transporters and by activation of the type 1 sodium proton exchanger. The resulting increased intracellular sodium promotes reversal of the astrocyte sodium-calcium exchanger creating an excess of intracellular calcium that ultimately leads to astrocyte death. We will test and refine these hypotheses using established cell culture injury models. We will subject cells to traumatic injury and manipulate various sodium and calcium transporters while measuring intracellular ion concentrations and cell viability. This information will be used to explore novel pharmacological manipulations targeted at these sodium and calcium injury mechanisms. In these in vivo therapeutic studies we will measure astrocyte and neuronal viability using anatomical markers, measure brain edema using magnetic resonance imaging, and measure functional outcome using behavioral measures of senscrimotor function and learning and memory following traumatic brain injury in the rat. PERFORMANCE SITE ========================================Section End===========================================