Liu Xiao-hong, Zhao Yong-li, Ma Qiao-mei, Zhou Xi-hui, Wang Yan
Department of Pediatrics, First Affiliated Hospital, Xi'an Jiaotong University, Xi'an 710061, China.
Zhonghua Er Ke Za Zhi. 2006 Mar;44(3):177-81.
Hyperbaric oxygenation (HBO) is an attractive procedure that has been used in treatment of hypoxic-ischemic encephalopathy (HIE). However, depending on the HBO protocol, especially the time point of starting treatment of HBO, different and conflicting results were obtained. This study was undertaken to search for the optimal therapeutic window of ABO in neonatal rat with hypoxic-ischemic brain damage (HIBD).
Eighty-four healthy seven-day-old SD rats were used as research subjects and were randomly divided into seven groups with 12 in each: sham group, HI group, HI (1 h) + HBO group (HBO starting 1 h after HI), HI (3 h) + HBO group (HBO starting 3 h after HI), HI (6 h) + HBO group (HBO starting 6 h after HI), HI (12 h) + HBO group (HBO starting 12 h after HI), HI (24 h) + HBO group (HBO starting 24 h after HI). Single HBO treatment (2.5 atmospheres absolute, ATA for 1.5 h) was used in this study. Two indexes were used to assess the effect of HBO that included short-term (48 h after HI) histology change (the cell density in CA1 of hippocampus and cortex) and long-term (5 w and 6 w after HI) neurobehavioral testing (grip test and treadmill test for evaluating the deficits of sensor motor; step-down avoidance test for assessing the deficits of memory).
In HI (1 h) + HBO, HI (3 h) + HBO and HI (6 h) + HBO groups, neuron density of cortex and CA1 of hippocampus were 1981.76 +/- 299.55, 1841.53 +/- 241.21, 1525.78 +/- 189.00 and 4430.56 +/- 1180.31, 4507.54 +/- 1374.32, 3883.48 +/- 821.87, respectively, which were significantly higher than HIBD group (987.86 +/- 285.39 and 1813.59 +/- 295.33, P < 0.05, ANOVA). But in HI (12 h) + HBO and HI (24 h) + HBO, the neuron density of cortex and CA1 of hippocampus compared with those in HIBD group had no statistical significance (P > 0.05, ANOVA). In the sensor motor testing performed at 5 w after HI of rat, the grip time in grip test and the stay time in treadmill test of HI (1 h) + HBO, HI (3 h) + HBO and HI (6 h) + HBO groups were 193.39 +/- 51.19, 168.39 +/- 34.02, 168.95 +/- 34.93 and 130.34 +/- 42.56, 128.20 +/- 27.69, 125.74 +/- 36.99, respectively, which, compared with HIBD group, were significantly prolonged (P < 0.05, ANOVA). But in HI (12 h) + HBO and HI (24 h) + HBO groups, the time was not significantly longer compared with HI (P > 0.05, ANOVA). In the step-down avoidance test which was performed at 6 w after HI, the step-down latencies of HI (1 h) + HBO, HI (3 h) + HBO and HI (6 h) + HBO were 96.91 +/- 29.91, 90.35 +/- 28.44 and 76.46 +/- 38.70, respectively, which were significantly prolonged (P < 0.05, ANOVA), but in HI (12 h) + HBO and HI (24 h) + HBO, the latencies did not significantly increase compared with HIBD, P > 0.05, ANOVA.
The optimal therapeutic window of HBO in neonatal rat with HIBD was within the first 6 hours after HI. In this therapeutic window, HBO was highly effective in reducing the cell loss in CA1 of hippocampus and cortex.
高压氧治疗（HBO）是一种用于治疗缺氧缺血性脑病（HIE）的有吸引力的方法。然而，根据HBO方案，尤其是开始HBO治疗的时间点，会得到不同且相互矛盾的结果。本研究旨在寻找新生大鼠缺氧缺血性脑损伤（HIBD）中HBO的最佳治疗窗。
84只健康7日龄SD大鼠作为研究对象，随机分为7组，每组12只：假手术组、HI组、HI（1小时）+HBO组（HI后1小时开始HBO）、HI（3小时）+HBO组（HI后3小时开始HBO）、HI（6小时）+HBO组（HI后6小时开始HBO）、HI（12小时）+HBO组（HI后12小时开始HBO）、HI（24小时）+HBO组（HI后24小时开始HBO）。本研究采用单次HBO治疗（绝对压力2.5个大气压，1.5小时）。采用两个指标评估HBO的效果，包括短期（HI后48小时）组织学变化（海马体CA1区和皮质的细胞密度）和长期（HI后5周和6周）神经行为测试（握力测试和跑步机测试以评估感觉运动缺陷；台阶回避测试以评估记忆缺陷）。
在HI（1小时）+HBO、HI（3小时）+HBO和HI（6小时）+HBO组中，皮质和海马体CA1区的神经元密度分别为1981.76±299.55、1841.53±241.21、1525.78±189.00和4430.56±1180.31、4507.54±1374.32、3883.48±821.87，显著高于HIBD组（987.86±285.39和1813.59±295.33，P<0.05，方差分析）。但在HI（12小时）+HBO和HI（24小时）+HBO组中，皮质和海马体CA1区的神经元密度与HIBD组相比无统计学意义（P>0.05，方差分析）。在大鼠HI后5周进行的感觉运动测试中，HI（1小时）+HBO、HI（3小时）+HBO和HI（6小时）+HBO组在握力测试中的握力时间和跑步机测试中的停留时间分别为193.39±51.19、168.39±34.02、168.95±34.93和130.34±42.56、128.20±27.69、125.74±36.99，与HIBD组相比显著延长（P<0.05，方差分析）。但在HI（12小时）+HBO和HI（24小时）+HBO组中，与HI相比时间延长不显著（P>0.05，方差分析）。在HI后6周进行的台阶回避测试中，HI（1小时）+HBO、HI（3小时）+HBO和HI（6小时）+HBO的台阶回避潜伏期分别为96.91±29.91、90.35±28.44和76.46±38.70，显著延长（P<0.05，方差分析），但在HI（12小时）+HBO和HI（24小时）+HBO组中，潜伏期与HIBD组相比无显著增加，P>0.05，方差分析。
新生大鼠HIBD中HBO的最佳治疗窗在HI后的前6小时内。在此治疗窗内，HBO在减少海马体CA1区和皮质的细胞损失方面非常有效。
