Jatana Manu, Singh Inderjit, Singh Avtar K, Jenkins Dorothea
Department of Pediatrics, Medical University of South Carolina, Charleston, SC 29425, USA.
Pediatr Res. 2006 May;59(5):684-9. doi: 10.1203/01.pdr.0000215045.91122.44.
Hypoxic ischemic (HI) injury in neonates may have devastating, long-term consequences. Recently completed clinical trials in HI neonates indicate that hypothermia within 6 h of birth results in modest improvement in the combined outcome of death or severe disability. The aim of this study was to investigate the effects of combining hypothermia and N-acetylcysteine (NAC) on brain injury, neonatal reflexes and myelination after neonatal HI. Seven-day-old rats were subjected to right common carotid artery ligation and hypoxia (8% oxygen) for 2 h. Systemic hypothermia (30 + 0.5 degrees C) was induced immediately after the period of HI and was maintained for 2 h. NAC (50 mg/kg) was administered by intraperitoneal injection daily until sacrifice. Brain infarct volumes were significantly reduced at 48 h post-HI in the hypothermia plus NAC group (21.5 +/- 3.84 mm3) compared with vehicle (240.85 +/- 4.08 mm3). Neonatal reflexes were also significantly improved by combination therapy at days 1 and 7. There was a significant loss of right hemispheric brain volume in the untreated group at 2 and 4 wk after HI insult. Brain volumes were preserved in hypothermia plus NAC group and were not significantly different when compared with the sham group. Similarly, increased myelin expression was seen in brain sections from hypothermia plus NAC group, when stained for Luxol Fast Blue (LFB), Myelin Basic Protein (MBP) and Proteolipid protein (PLP). These results indicate that hypothermia plus NAC combination therapy improves infarct volume, myelin expression and functional outcomes after focal HI injury.
新生儿缺氧缺血性（HI）损伤可能会产生毁灭性的长期后果。最近完成的针对HI新生儿的临床试验表明，出生后6小时内进行低温治疗可使死亡或严重残疾的综合结局得到适度改善。本研究的目的是探讨低温与N-乙酰半胱氨酸（NAC）联合应用对新生儿HI后脑损伤、新生儿反射和髓鞘形成的影响。7日龄大鼠接受右侧颈总动脉结扎并缺氧（8%氧气）2小时。HI期结束后立即诱导全身低温（30±0.5摄氏度），并维持2小时。每天腹腔注射NAC（50mg/kg）直至处死。与对照组（240.85±4.08mm³）相比，低温加NAC组在HI后48小时脑梗死体积显著减小（21.5±3.84mm³）。联合治疗在第1天和第7天也显著改善了新生儿反射。HI损伤后2周和4周，未治疗组右侧半球脑体积显著减少。低温加NAC组脑体积得以保留，与假手术组相比无显著差异。同样，当用卢戈氏碘蓝（LFB）、髓鞘碱性蛋白（MBP）和蛋白脂蛋白（PLP）染色时，低温加NAC组脑切片中可见髓鞘表达增加。这些结果表明，低温加NAC联合治疗可改善局灶性HI损伤后的梗死体积、髓鞘表达和功能结局。
