Puka-Sundvall M, Sandberg M, Hagberg H
Dept. of Anatomy and Cell Biology, Univ. of Göteborg, Box 420, 405 30 Göteborg, Sweden.
Brain Res. 1998 Jun 29;797(2):328-32. doi: 10.1016/s0006-8993(98)00415-6.
The aim of this study was to investigate the role of cysteine in development of brain damage after hypoxia-ischemia (HI) in neonatal rats. Rat pups were subjected to unilateral carotid ligation and exposure to hypoxia (7.7% oxygen) for 60 or 90 min. A subtoxic dose of cysteine were administered before or after HI and the unilateral brain injury was evaluated 14 days after the insult and expressed as ipsilateral weight deficit as % of the contralateral hemisphere. In some experiments the changes of extracellular (e.c.) cysteine in the cerebral cortex were sampled with microdialysis and analyzed with HPLC. Cysteine in a dose of 0.2 mg/g s.c. given before 60 min of HI increased the extent of brain injury by 59%. The effect of posttreatment was limited and dependent on the duration of HI: 0.2 mg/g of cysteine given after 90 min of HI increased the degree of brain injury by 25%, whereas the same dose administered after 60 min of HI was ineffective in spite of that this combination of cysteine and HI resulted in e.c. cysteine concentrations 3-4 times higher than those observed in non-treated HI controls. These data show that subtoxic doses of cysteine administered before or after HI enhances brain injury. However, e.c. cysteine levels exceeding those induced by HI are required which makes a substantial contribution of cysteine in the pathophysiology of HI brain injury in the neonatal rat unlikely.
本研究的目的是探讨半胱氨酸在新生大鼠缺氧缺血（HI）后脑损伤发展中的作用。将幼鼠进行单侧颈动脉结扎，并暴露于低氧环境（7.7%氧气）60或90分钟。在HI之前或之后给予亚毒性剂量的半胱氨酸，并在损伤后14天评估单侧脑损伤情况，以同侧体重缺损占对侧半球的百分比表示。在一些实验中，用微透析采集大脑皮质细胞外（e.c.）半胱氨酸的变化，并通过高效液相色谱法进行分析。在HI 60分钟前皮下注射0.2 mg/g的半胱氨酸会使脑损伤程度增加59%。治疗后效果有限且取决于HI的持续时间：在HI 90分钟后给予0.2 mg/g的半胱氨酸会使脑损伤程度增加25%，而在HI 60分钟后给予相同剂量则无效，尽管半胱氨酸和HI的这种组合导致细胞外半胱氨酸浓度比未治疗的HI对照组高3 - 4倍。这些数据表明，在HI之前或之后给予亚毒性剂量的半胱氨酸会加重脑损伤。然而，需要细胞外半胱氨酸水平超过HI诱导的水平，这使得半胱氨酸在新生大鼠HI脑损伤病理生理学中起重大作用的可能性不大。
