BASIS OF MRS SIGNALS AFTER TRAUMATIC BRAIN INJURY

描述（改编自申请人？（摘要）：本项目的总体目标 项目是确定神经化学标志物的生理基础， 质子磁共振波谱（IH-MRS）在颅脑损伤中的应用 长期目标是改善TBI患者的治疗。 TBI具有广泛的经济和社会影响， 临床数据仍然不可靠。研究人员在人类 研究表明，脑损伤、代谢性抑郁和 用（1）H-MRS测量炎症高度预测认知功能 结果。然而，潜在的生理事件，连接细胞损失和 代谢异常与MRS变化的关系尚不清楚。使用一个完善的 在大鼠TBI的挫伤模型中，他们将测量 N-乙酰天冬氨酸（NAA，一种在 浓度类似于神经元中的谷氨酸盐， 对神经元损伤敏感）和胆碱（Cho -膜损伤的标志物 和炎症）在急性期（约1小时）至慢性期 在纵向研究中，TBI后28天阶段。的相对贡献 脑血流量（CBF）的变化，细胞死亡和代谢抑制， 将通过比较MRS信号与3D图像来确定NAA信号 CBF变化的测量与灌注MR，细胞死亡的确定 组织学和代谢抑制，以确定与细胞色素 氧化酶技术预计NAA水平的降低和最终恢复 在TBI之后，也将与细胞生理测量相关， 确定NAA预测认知功能的功能基础 结果，通过测量内在和网络神经元的兴奋性， 电压敏感性染料，并通过测量细胞内的钙调节 用荧光技术在不同的时间点，从4小时到 28天最初将在体外切片上进行测量 在进行MRS测量后从动物获得的制备物。在 在以后的研究中，该研究将在体内用双光子扫描激光进行 显微镜Cho和MRS可见脂质的变化与以下因素有关： 巨噬细胞/小胶质细胞消化膜和水肿。他们预计 这些方法的结合将提供重要的新信息， 脑外伤后MRS谱的细胞基础这应该是 最终在病人管理和新的发展有价值 治疗TBI的干预措施。

DESCRIPTION (Adapted from the applicant?s abstract): The overall goal of this project is to determine the physiological bases for neurochernical markers of brain injury seen with proton Magnetic Resonance Spectroscopy (IH-MRS) in TBI patients with a long-term goal of improving the treatment of TBI patients. TBI has widespread economic and social impact, and yet prognostication based on clinical data is still unreliable. The investigators have shown in human studies that neurochemical markers of brain injury, metabolic depression, and inflammation measured with (1)H-MRS are highly predictive of cognitive outcome. However, the underlying physiological events that link cell loss and metabolic abnormalities to MRS changes are poorly understood. Using a well-established contusion model of TBI in the rat, they will measure the time courses of changes in N-acetylaspartate (NAA, an amino acid found at concentrations similar to glutamate in the neuron and which is highly sensitive to neuronal injury) and choline (Cho -a marker of membrane injury and inflammation) during the acute phase (about one hr) up to the chronic phase of 28 days post TBI in a longitudinal study. The relative contributions of cerebral blood flow (CBF) changes, cell death and metabolic depression to NAA signals will be determined by comparing the MRS signals with the 3D images of CBF changes to be measured with perfusion MR, cell death to be determined histologically and metabolic depression to be determined with the cytochrome oxidase technique. The reduction and eventual recovery in NAA level expected after a TBI will be also related to cellular physiological measures in order to determine functional bases for the ability of NAA to predict cognitive outcome, by measuring intrinsic and network neuronal excitability with voltage-sensitive dyes, and by measuring the intracellular regulation of Ca2+ with fluorescence techniques at different time points ranging from four hrs to 28 days. The measurements will be carried out initially on in vitro slice preparations obtained from the animals after performing MRS measurements. In later studies, the study will be done in vivo with a two-photon scanning laser microscope. The changes in Cho and MRS-visible lipids will be related to macrophage/microglia digestion of membranes and to edema. They anticipate that the combination of approaches will provide important new information about the cellular basis for MRS profiles after TBI. This should be eventually valuable in patient management and the development of new intervention for treatment of TBI.