Mimicking partial to total placental insufficiency in a rabbit model of cerebral palsy.

Mimicking partial to total placental insufficiency in a rabbit model of cerebral palsy.
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DOI:
10.1002/jnr.24901
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发表时间:
2022-12
影响因子:
4.2
通讯作者:
Tan S
Tan S
中科院分区:
医学3区
文献类型:
--
作者:
Shi Z;Luo K;Jani S;February M;Fernandes N;Venkatesh N;Sharif N;Tan S

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所有胎盘早剥都始于部分早剥,有时表现为胎儿心动过缓。我们用一种新的兔胎盘功能不全模型模拟了从部分胎盘剥离到完全胎盘早剥的过程,并用足够的统计能力将其与先前模拟完全胎盘早剥的模型进行了比较。先前的模型使用妊娠新西兰大白兔E22或E25(分别为70%或79%)的全子宫缺血,持续40min(全H-I)。新的模型,部分+完全H-I,在40分钟全缺血之前增加了30分钟的部分缺血。胎儿要么在E31.5(足月)经阴道分娩进行神经行为测试,要么在E25通过剖腹产进行体外脑细胞活性评估。胎儿心动过缓发生在两种H-I方案的前2分钟内。在E22和E25死亡或严重感染试剂盒(76%比79%)、E25正常试剂盒(66%比%)和任何年龄的单个新生儿神经行为测试中,完全H-I组(n=442例E22,E25组312例)和部分+完全H-I组(n=154和80例)之间没有差异。未发现性别差异。在所研究的脑区中,72小时后部分+完全缺氧(n=6)的细胞存活率低于完全缺氧(n=8)。部分+完全H-I损伤产生的脑瘫表型与我们之前在一项充分有效的研究中建立的完全H-I模型相似,可能更适合于测试潜在的神经保护剂。
All placental abruptions begin as partial abruptions, which sometimes manifest as fetal bradycardia. The progression from partial to total abruption was mimicked by a new rabbit model of placental insufficiency, and we compared it, with sufficient statistical power, with the previous model mimicking total placental abruption. The previous model uses total uterine ischemia at E22 or E25 (70% or 79% term, respectively), in pregnant New Zealand white rabbits for 40 min (Full H-I). The new model, Partial+Full H-I, added a 30-min partial ischemia before the 40-min total ischemia. Fetuses were delivered either at E31.5 (full term) vaginally for neurobehavior testing, or by C-section at E25 for ex-vivo brain cell-viability evaluation. The onset of fetal bradycardia was within the first 2 minutes of either H-I protocol. There was no difference between Full H-I (n=442 for E22, 312 for E25) and Partial+Full H-I (n=154 and 80) groups in death or severely affected kits at E22 (76% vs 79%) or at E25 (66% vs 64%), or normal kits at E22 or E25, or any of the individual newborn neurobehavioral tests at any age. No sex differences were found. Partial+Full H-I (n=6) showed less cell viability than Full H-I (n=8) at 72-hr ex vivo in the brain regions studied. Partial+Full H-I insult produced similar cerebral palsy phenotype as our previous Full H-I model in a sufficiently powered study and may be more suitable for testing of potential neuroprotectants.
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