Neonatal hypoxic-ischemic brain injury is commonly studied by means of the Vannucci procedure in mice or rats (unilateral common carotid artery occlusion followed by hypoxia). Previously, we modified the postnatal day 7 (P7) rat procedure for use in mice, and later demonstrated that genetic strain strongly influences the degree of brain injury in the P7 mouse model of hypoxia-ischemia (HI). Recently, the P9 or P10 mouse brain was recognized as the developmental equivalent of a term neonatal human brain, rather than P7. Consequently, the Vannucci procedure has again been modified, and a commonly used protocol employs 10% oxygen for 50 min in C57Bl/6 mice. Strain differences have yet to be described for the P9/P10 mouse model. In order to determine if the strain differences we previously reported in the P7 mouse model are present in the P9 model, we compared 2 commonly used strains, CD1 and C57Bl/6J, in both the P7 (carotid ligation [in this case, right] followed by exposure to 8% oxygen for 30 min) and P9 (carotid ligation [in this case left] followed by exposure to 10% oxygen) models of HI. Experiments using the P7 model were performed in 2001-2012 and those using the P9 model were performed in 2012-2016. Five to seven days after the HI procedure, mice were perfused with 4% paraformaldehyde, their brains were sectioned on a Vibratome (50 µm) and alternate sections were stained with Perl's iron stain or cresyl violet. Brain sections were examined microscopically and scored for the degree of injury. Since brains in the P7 group had been scored previously with a slightly different system, they were reanalyzed using our current scoring system which scores injury in 11 regions: the anterior, middle, and posterior cortex; the anterior, middle, and posterior striatum; CA1, CA2, CA3, and the dentate gyrus of the hippocampus and thalamus, on a scale from 0 (none) to 3 (cystic infarct) for a total score of 0-33. Brains in the P9 group were scored with the same system. Given the same insult, the P7 CD1 mice had greater injury than the C57Bl/6J mice, which agrees with our previous findings. The P9 CD1 mice also had greater injury than the C57Bl/6J mice. This study confirms that CD1 mice are more susceptible to injury than C57Bl/6J mice and that strain selection is important when using mouse models of HI.

中文翻译：

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小鼠新生儿缺氧缺血中的菌株相关差异。

新生儿缺氧缺血性脑损伤通常通过Vannucci程序在小鼠或大鼠中进行研究（单侧颈总动脉闭塞，然后缺氧）。以前，我们修改了小鼠出生后第7天（P7）大鼠的操作程序，后来证明遗传应变严重影响缺氧缺血（HI）的P7小鼠模型的脑损伤程度。最近，P9或P10小鼠的大脑被认为是术语新生儿人类大脑的发育等效物，而不是P7。因此，再次对Vannucci程序进行了修改，并且在C57Bl / 6小鼠中常用的方案是在10分钟内使用10％的氧气。对于P9 / P10鼠标模型，尚需描述应变差异。为了确定我们先前在P7小鼠模型中报告的应变差异是否存在于P9模型中，我们比较了两种常用的菌株CD1和C57Bl / 6J，它们分别在P7（颈动脉结扎[在这种情况下，右]然后暴露于8％的氧气中30分钟）和P9（在颈动脉结扎[在这种情况下，左]暴露于10％的HI模型中。使用P7模型的实验在2001-2012年进行，使用P9模型的实验在2012-2016年进行。HI手术后5至7天，给小鼠灌注4％多聚甲醛，将其大脑切成Vibratome（50 µm）切片，并用Perl的铁染剂或甲酚紫染色。显微镜下检查脑切片，并对损伤程度进行评分。由于P7组的大脑之前曾使用略有不同的系统评分，因此使用我们目前的评分系统对它们进行了重新分析，该评分系统在11个区域评分：前，中和后皮质；前，中和后纹状体; CA1，CA2，CA3以及海马和丘脑的齿状回，范围从0（无）到3（囊性梗塞），总分为0-33。P9组的大脑使用相同的系统评分。同样的侮辱，P7 CD1小鼠比C57Bl / 6J小鼠具有更大的损伤，这与我们以前的发现是一致的。P9 CD1小鼠也比C57Bl / 6J小鼠具有更大的损伤。这项研究证实，CD1小鼠比C57Bl / 6J小鼠更容易受到伤害，并且在使用HI小鼠模型时，品系选择很重要。P9组的大脑使用相同的系统评分。同样的侮辱，P7 CD1小鼠比C57Bl / 6J小鼠具有更大的损伤，这与我们以前的发现是一致的。P9 CD1小鼠也比C57Bl / 6J小鼠具有更大的损伤。这项研究证实，CD1小鼠比C57Bl / 6J小鼠更容易受到伤害，并且在使用HI小鼠模型时，品系选择很重要。P9组的大脑使用相同的系统评分。同样的侮辱，P7 CD1小鼠比C57Bl / 6J小鼠具有更大的损伤，这与我们以前的发现是一致的。P9 CD1小鼠也比C57Bl / 6J小鼠具有更大的损伤。这项研究证实，CD1小鼠比C57Bl / 6J小鼠更容易受到伤害，并且在使用HI小鼠模型时，品系选择很重要。