Department of Physiology and Pharmacology, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA.
Transl Stroke Res. 2011 Sep 1;2(3):382-90. doi: 10.1007/s12975-011-0081-5.
The neonatal hypoxia-ischemia rat model referred to as the Rice-Vannucci model is extensively used to study perinatal hypoxia-ischemia and child brain injury. One of the major weaknesses of this model is its inconsistency of brain infarction among animals. We hypothesize that the inconsistency of infarction is caused by prolonged operation time and therefore isoflurane exposure. Neonatal hypoxia-ischemia was induced in postnatal days 7 and 10 rat pups by unilateral right common carotid ligation followed by 2.5 h of hypoxia (8% oxygen). The incision-to-ligation (ITL) was defined as the amount of time from initial incision (4 min after 2% isoflurane exposure) to completion of carotid ligation (at which point isoflurane exposure was also terminated). In the first part of the study, the ITL of each group was designated to be 5, 13, and 21 min. In the second part of the study, the ITL is designated to 4 min; however, continued isoflurane was used to make 5, 13, and 21 min isoflurane exposure for each group. Percentages of brain infarction were assessed at 48 h following surgery. Motor deficits were accessed by Rotarod test. Marked brain infarction was observed in the 5-min ITL group and a decrease of brain infarction observed in the 13-and 21-min groups (P<0.05). In the second part of the study, marked brain infarction was observed in the 5-min isoflurane exposure group, and a decrease of brain infarction was observed in each of the 13- and 21-min isoflurane exposure groups (P<0.05). Similar tendencies were observed in Rotarod tests than 5-min ITL and 5-min isoflurane groups showed more marked deficits (P<0.05). This study demonstrated that brain infarction inconsistency of the neonatal hypoxia-ischemia rat pup model is related to the operation time. The observed time-dependent decrease of brain infarction is correlated to the isoflurane exposure time. Shorter operation and isoflurane exposure improves this model consistency of brain infarction and motor deficits.
用于研究围产期缺氧缺血和儿童脑损伤的新生大鼠缺氧缺血模型，通常被称为 Rice-Vannucci 模型。该模型的一个主要缺点是其脑梗死在动物之间的不一致性。我们假设这种不一致性是由手术时间延长和异氟醚暴露引起的。在新生后 7 天和 10 天的大鼠幼仔中，通过单侧右颈总动脉结扎，然后进行 2.5 小时的缺氧（8%氧气）诱导新生大鼠缺氧缺血。手术时间（ITL）定义为从初始切口（2%异氟醚暴露 4 分钟后）到完成颈总动脉结扎的时间（此时异氟醚暴露也结束）。在研究的第一部分中，每组的 ITL 指定为 5、13 和 21 分钟。在研究的第二部分中，ITL 被指定为 4 分钟；然而，继续使用异氟醚为每组进行 5、13 和 21 分钟的异氟醚暴露。术后 48 小时评估脑梗死百分比。通过转棒试验评估运动缺陷。在 5 分钟 ITL 组观察到明显的脑梗死，在 13 和 21 分钟组观察到脑梗死减少（P<0.05）。在研究的第二部分中，在 5 分钟异氟醚暴露组观察到明显的脑梗死，在每个 13 和 21 分钟异氟醚暴露组观察到脑梗死减少（P<0.05）。在转棒试验中观察到了类似的趋势，与 5 分钟 ITL 和 5 分钟异氟醚组相比，显示出更明显的缺陷（P<0.05）。本研究表明，新生大鼠缺氧缺血模型的脑梗死不一致性与手术时间有关。观察到的脑梗死时间依赖性减少与异氟醚暴露时间有关。缩短手术和异氟醚暴露时间可提高该模型脑梗死和运动缺陷的一致性。
