BASIS OF MRS SIGNALS AFTER TRAUMATIC BRAIN INJURY

描述(改编自申请者？S摘要)：本次活动的总体目标 项目是确定神经干细胞标记物的生理学基础。 脑损伤的质子磁共振波谱(IH-MRS)研究 患者的长期目标是改善对脑外伤患者的治疗。 TBI具有广泛的经济和社会影响，但基于预测 关于临床数据的数据仍然不可靠。研究人员已经在人类中展示了 脑损伤的神经化学标志物、代谢抑制和 用(1)H-MRS测量炎症反应高度预测认知功能 结果。然而，连接细胞丢失和细胞死亡的潜在生理事件 代谢异常对MRS的改变知之甚少。使用一种成熟的 在大鼠脑挫裂伤模型上，他们将测量时间 N-乙酰天冬氨酸(NAA)的变化过程，这是一种在 神经元中类似谷氨酸的浓度，它是高度 对神经元损伤敏感)和胆碱(CHO--膜损伤的标志 和炎症)在急性期(约一小时)到慢性 一项关于颅脑损伤后28天阶段的纵向研究。相对贡献率 脑血流量(CBF)变化、细胞死亡和代谢抑制 将通过将MRS信号与3D图像进行比较来确定NAA信号 脑血流量变化需用磁共振灌注成像测量，细胞死亡有待确定 组织学和代谢抑制用细胞色素测定 氧化酶法。预计NAA水平将下降并最终恢复 脑损伤后还将按细胞生理指标顺序进行测定 确定NAA预测认知能力的功能基础 结果，通过测量固有的和网络的神经元兴奋性 电压敏感染料，并通过测量细胞内钙离子的调节 在不同的时间点使用荧光技术，从四小时到 28天。测量最初将在体外切片上进行 在进行MRS测量后从动物身上获得的准备。在……里面 在以后的研究中，这项研究将在活体内使用双光子扫描激光进行 显微镜。CHO和MRS可见血脂的变化将与 巨噬细胞/小胶质细胞消化膜而致水肿。他们期待着 这些方法的结合将提供重要的新信息 关于颅脑损伤后磁共振波谱的细胞基础。这应该是 最终在患者管理和新的开发方面有价值 颅脑损伤的干预治疗。

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.