Hobbs Catherine E, Murphy Michael P, Smith Robin A J, Oorschot Dorothy E
Department of Anatomy and Structural Biology, University Otago, Dunedin, New Zealand.
Pediatr Int. 2008 Aug;50(4):481-8. doi: 10.1111/j.1442-200X.2008.02705.x.
The production of oxygen free radicals after perinatal hypoxia-ischemia is thought to play a critical role in the pathogenesis of the brain injury. Administration of anti-oxidants may thus be neuroprotective. The aim of the present study was to investigate the effect of a mitochondria-targeted anti-oxidant mitoquinol (mitoQ) administered in the form of the prodrug mitoquinone, and an extracellular anti-oxidant N-tert-butyl-(2-sulfophenyl)-nitrone (S-PBN; Aldrich, St Louis, MO, USA), on neuronal survival in the rat striatum after acute perinatal hypoxia-ischemia.
Mitoquinone at 17 micromol/L (n = 6) or 51 micromol/L (n = 6), or its diluent (n = 12), was continuously infused over 3 days into the right striatum of Sprague-Dawley rats. Infusion was via an Alzet micro-osmotic pump (Alza, Los Angeles, CA, USA), stereotaxically implanted on postnatal day (PN) 7 under anesthesia. In another experiment, S-PBN (100 mg/kg) (n = 8) or its diluent (n = 8) was administered in six s.c. injections every 12 h from the evening of PN7. Hypoxia-ischemia was induced on PN8 by right common carotid artery ligation under anesthesia, followed 2.5 h later by exposure to 8% oxygen for 1.5 h. On PN14 the pups were euthanased and 40 microm serial sections were cut through the entire striatum. The total number of medium-spiny neurons within the right striatum was stereologically determined using the optical disector/Cavalieri method.
No significant difference was seen in the total number of striatal medium-spiny neurons between the 17 micromol/L or 51 micromol/L mitoQ-treated pups and their respective diluent-treated controls. No significant difference was seen in the total number of striatal medium-spiny neurons between the S-PBN-treated and diluent-treated pups.
Solely targeting mitochondrial oxidants with mitoQ, or extracellular oxidants with S-PBN, is not protective for striatal medium-spiny neurons after perinatal hypoxia-ischemia.
围产期缺氧缺血后氧自由基的产生被认为在脑损伤的发病机制中起关键作用。因此，给予抗氧化剂可能具有神经保护作用。本研究的目的是探讨以前药米托醌形式给药的线粒体靶向抗氧化剂米托醌（mitoQ）和细胞外抗氧化剂N-叔丁基-（2-磺苯基）-硝酮（S-PBN；美国密苏里州圣路易斯市奥德里奇公司）对急性围产期缺氧缺血后大鼠纹状体神经元存活的影响。
将17微摩尔/升（n = 6）或51微摩尔/升（n = 6）的米托醌或其稀释剂（n = 12）在3天内持续注入Sprague-Dawley大鼠的右侧纹状体。通过立体定位植入在出生后第7天（PN7）麻醉状态下的Alzet微渗透泵（美国加利福尼亚州洛杉矶市阿尔扎公司）进行输注。在另一项实验中，从PN7傍晚开始，每12小时皮下注射6次S-PBN（100毫克/千克）（n = 8）或其稀释剂（n = 8）。在PN8时，通过麻醉下结扎右侧颈总动脉诱导缺氧缺血，2.5小时后再暴露于8%氧气中1.5小时。在PN14时对幼崽实施安乐死，并对整个纹状体进行40微米连续切片。使用光学分割器/卡瓦列里方法对右侧纹状体内中等棘状神经元的总数进行立体测定。
17微摩尔/升或51微摩尔/升米托醌处理的幼崽与其各自稀释剂处理的对照组之间，纹状体中等棘状神经元的总数没有显著差异。S-PBN处理的幼崽与稀释剂处理的幼崽之间，纹状体中等棘状神经元的总数也没有显著差异。
单独用米托醌靶向线粒体氧化剂或用S-PBN靶向细胞外氧化剂，对围产期缺氧缺血后的纹状体中等棘状神经元没有保护作用。
