Andiné P, Sandberg M, Bågenholm R, Lehmann A, Hagberg H
Institute of Neurobiology, University of Göteborg, Sweden.
Brain Res Dev Brain Res. 1991 Dec 17;64(1-2):115-20. doi: 10.1016/0165-3806(91)90214-4.
Excitatory amino acids (EAAs) have been implicated to play a part in the development of hypoxic-ischemic brain injury in the neonate. The aim of the present study was to follow changes of intra- and extracellular (microdialysis) amino acids in the cerebral cortex in a model where cortical hypoxic-ischemic damage is produced consistently. Hypoxic-ischemia (unilateral ligation of the carotid artery + 2 h of exposure to 7.8% oxygen) caused a depletion of tissue ATP, phosphocreatine and glucose with a concomittant accumulation of AMP and lactic acid in cortical tissue. These changes were accompanied by a decrease of tissue aspartate and glutamine whereas the contents of gamma-aminobutyric acid (GABA), phenylalanine, leucine, isoleucine, valine and alanine increased. In the extracellular fluid GABA, glutamate, aspartate, taurine, glycine and alanine all increased multi-fold during hypoxic-ischemia. Aspartate and glutamate returned to near initial levels 2 h after the end of the insult, whereas the elevation of glycine persisted during recovery. In conclusion, the high extracellular levels of EAAs and glycine may exert injurious effects during and after hypoxic-ischemia.
兴奋性氨基酸（EAAs）被认为在新生儿缺氧缺血性脑损伤的发展中起作用。本研究的目的是在一个能持续产生皮质缺氧缺血性损伤的模型中，追踪大脑皮质内和细胞外（微透析）氨基酸的变化。缺氧缺血（单侧颈动脉结扎 + 暴露于7.8%氧气中2小时）导致皮质组织中三磷酸腺苷（ATP）、磷酸肌酸和葡萄糖耗竭，同时伴随腺苷一磷酸（AMP）和乳酸在皮质组织中的积累。这些变化伴随着组织中天冬氨酸和谷氨酰胺的减少，而γ-氨基丁酸（GABA）、苯丙氨酸、亮氨酸、异亮氨酸、缬氨酸和丙氨酸的含量增加。在细胞外液中，GABA、谷氨酸、天冬氨酸、牛磺酸、甘氨酸和丙氨酸在缺氧缺血期间均增加了数倍。天冬氨酸和谷氨酸在损伤结束后2小时恢复到接近初始水平，而甘氨酸的升高在恢复过程中持续存在。总之，兴奋性氨基酸和甘氨酸的高细胞外水平可能在缺氧缺血期间及之后发挥损伤作用。
