Abstract:
Brain health is largely dependent on the metabolic regulation of amino acids. Brain injuries, diseases, and disorders can be detected through alterations in free amino acid (FAA) concentrations; and thus, mapping the changes has high diagnostic potential. Common methods focus on optimizing neurotransmitter quantification; however, recent focus has expanded to investigate the roles of molecular precursors in brain metabolism. An isocratic method using high performance liquid chromatography with electrochemical cell detection was developed to quantify a wide range of molecular precursors and neurotransmitters: alanine, arginine, aspartate, serine, taurine, threonine, tyrosine, glycine, glutamate, glutamine, and γ-Aminobutyric acid (GABA) following traumatic brain injury. First, baseline concentrations were determined in the serum, cerebrospinal fluid, hippocampus, cortex, and cerebellum of naïve male Sprague Dawley rats. A subsequent study was performed investigating acute changes in FAA concentrations following blast-induced traumatic brain injury (bTBI). Molecular precursor associated FAAs decreased in concentration at 4 h after injury in both the cortex and hippocampus while those serving as neurotransmitters remained unchanged. In particular, the influence of oxidative stress on the observed changes within alanine and arginine pathways following bTBI should be further investigated to elucidate the full therapeutic potential of these molecular precursors at acute time points.
摘要:
大脑健康很大程度上取决于氨基酸的代谢调节。脑损伤,疾病,和疾病可以通过游离氨基酸(FAA)浓度的变化来检测;因此,映射变化具有很高的诊断潜力。常见的方法集中在优化神经递质定量;然而,最近的焦点已经扩展到研究分子前体在脑代谢中的作用。开发了一种使用具有电化学电池检测的高效液相色谱的等度方法,以定量多种分子前体和神经递质:丙氨酸,精氨酸天冬氨酸,丝氨酸,牛磺酸,苏氨酸,酪氨酸,甘氨酸,谷氨酸,谷氨酰胺,创伤性脑损伤后的γ-氨基丁酸(GABA)。首先,在血清中测定基线浓度,脑脊液,海马体,皮质,和幼稚雄性SpragueDawley大鼠的小脑。进行了随后的研究,研究了爆炸诱发的创伤性脑损伤(bTBI)后FAA浓度的急性变化。损伤后4小时,皮质和海马中与分子前体相关的FAA浓度均下降,而作为神经递质的FAA则保持不变。特别是,应进一步研究氧化应激对bTBI后丙氨酸和精氨酸途径内观察到的变化的影响,以阐明这些分子前体在急性时间点的全部治疗潜力.