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.
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