Sonnewald Ursula, Kondziella Daniel
Department of Neuroscience, Norwegian University of Science and Technology (NTNU), Olav Kyrresgt. 3, NO-7489 Trondheim, Norway.
NMR Biomed. 2003 Oct-Nov;16(6-7):424-9. doi: 10.1002/nbm.837.
Nuclear magnetic resonance spectroscopy (NMRS) has been used extensively for several decades to elucidate metabolic pathways in biological systems and has led to new insights into cerebral metabolism. Many of these insights have been gained by NMRS using in vitro models, such as tissue extracts, cell cultures or brain slices. Extracts of cells or tissue provide an excellent basis for metabolic studies and facilitate the interpretation of in vivo spectra. (13)C NMRS is at present mostly used for in vitro or animal studies. Conclusions from the epilepsy models presented in this review are that turnover of metabolites is time-dependent in kainate-injected rats with limbic seizures. Early and only temporarily enhanced astrocytic activity is followed by altered metabolism in neurons with an increased turnover of important amino acids such as GABA and glutamate. However, pentylenetetrazole (PTZ) kindling affects astrocytes in younger and glutamatergic neurons in older animals. In the presence of PTZ, phenobarbital decreases labeling of most metabolites in all cell types, except GABAergic neurons, from both labeled precursors in the younger animals. However, in older animals only GABAergic neurons are affected by phenobarbital, as indicated by an increase in GABA labeling. In kaolin-induced hydrocephalus it was shown that astrocyte metabolism is disturbed in the early phase, particularly in the cerebrum. These alterations continue into the chronic period. Only then do the first signs of neuronal metabolic impairment appear, which might explain why dementia is a prominent clinical feature in patients with chronic hydrocephalus.
几十年来,核磁共振波谱法(NMRS)被广泛用于阐明生物系统中的代谢途径,并为脑代谢带来了新的见解。其中许多见解是通过使用体外模型的NMRS获得的,如组织提取物、细胞培养物或脑切片。细胞或组织提取物为代谢研究提供了良好的基础,并有助于体内光谱的解释。目前,(13)C NMRS主要用于体外或动物研究。本综述中提出的癫痫模型的结论是,在注射红藻氨酸引发边缘性癫痫的大鼠中,代谢物的周转是时间依赖性的。早期且仅暂时增强的星形胶质细胞活性之后,神经元代谢发生改变,重要氨基酸如GABA和谷氨酸的周转增加。然而,戊四氮(PTZ)点燃在年幼动物中影响星形胶质细胞,在年长动物中影响谷氨酸能神经元。在PTZ存在的情况下,苯巴比妥降低了年幼动物中所有细胞类型(除GABA能神经元外)从两种标记前体中获得的大多数代谢物的标记。然而,在年长动物中,只有GABA能神经元受到苯巴比妥的影响,这表现为GABA标记增加。在高岭土诱导的脑积水模型中,研究表明星形胶质细胞代谢在早期受到干扰,尤其是在大脑中。这些改变持续到慢性期。只有到那时,神经元代谢受损的最初迹象才会出现,这可能解释了为什么痴呆是慢性脑积水患者的一个突出临床特征。