Cherici G, Alesiani M, Pellegrini-Giampietro D E, Moroni F
Department of Preclinical and Clinical Pharmacology, University of Florence, Italy.
Brain Res Dev Brain Res. 1991 Jun 21;60(2):235-40. doi: 10.1016/0165-3806(91)90052-k.
Simulated ischemic conditions or a source of oxygen-derived free radicals, such as xanthine plus xanthine oxidase, released a significant amount of the excitotoxic amino acids Asp and Glu from adult rat hippocampal slices incubated in vitro. The concentrations of Asp and Glu in the incubation medium increased by 20 and 30 times respectively when such slices were exposed to simulated ischemia for a 10-min period. However, preparations obtained from 4- to 9-day-old rats did not release Asp or Glu either when exposed to ischemia or after K+ depolarization. This release appeared 10-15 days after birth and progressively increased up to 13 months of age. No further increase was observed in 25-month-old animals. The exposure of the slices to a source of oxygen-derived free radicals induced a release of excitotoxic amino acids independently from the age of the rats. The massive excitotoxic amino acid release from adult hippocampal slices and the formation of free radicals induced by ischemic insults has been previously associated with degeneration of hippocampal neurons. The lack of ischemia-induced excitotoxic amino acid release from the newborn hippocampus may help to explain why the newborn hippocampus is more resistant than the adult to hypoxic/ischemic insults.
模拟缺血条件或氧自由基来源,如黄嘌呤加黄嘌呤氧化酶,可使体外培养的成年大鼠海马切片释放大量兴奋性毒性氨基酸天冬氨酸(Asp)和谷氨酸(Glu)。当此类切片暴露于模拟缺血10分钟时,孵育培养基中天冬氨酸和谷氨酸的浓度分别增加了20倍和30倍。然而,从4至9日龄大鼠获得的切片在暴露于缺血时或钾离子去极化后均未释放天冬氨酸或谷氨酸。这种释放出生后10至15天出现,并在13个月龄前逐渐增加。在25月龄动物中未观察到进一步增加。将切片暴露于氧自由基来源会导致兴奋性毒性氨基酸的释放,这与大鼠年龄无关。成年海马切片大量释放兴奋性毒性氨基酸以及缺血性损伤诱导自由基形成,此前一直与海马神经元变性有关。新生海马缺乏缺血诱导的兴奋性毒性氨基酸释放,这可能有助于解释为什么新生海马比成年海马对缺氧/缺血性损伤更具抵抗力。