Effects of Three Different Doses of Inter-Alpha Inhibitor Proteins on Severe Hypoxia-Ischemia-Related Brain Injury in Neonatal Rats.
Effects of Three Different Doses of Inter-Alpha Inhibitor Proteins on Severe Hypoxia-Ischemia-Related Brain Injury in Neonatal Rats.
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DOI：
10.3390/ijms232113473
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发表时间：
2022-11-03
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
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缺氧缺血(HI)相关的脑损伤是新生儿发病和长期残疾的重要原因。我们先前已经证明，人血浆衍生的α-干扰素抑制蛋白(HIAIPs)可以减轻新生大鼠缺氧缺氧性脑损伤。HIAIP的神经保护作用和改善行为结果的最佳剂量仍有待确定。新生Wistar大鼠出生后7天(P7)分别给予30、60、90 mg/kg的HIAIPs，造成假手术或单侧HI(8%O2，2 h)脑损伤。分别于缺氧缺血后0、24、48h腹腔注射安慰剂、30、60、90 mg/kg的HIAIPs(n=9~10/性别)。我们进行了以下行为分析：P8(翻正反射)、P9(负向趋地性)和P10(开场任务)。在第10天处死大鼠，用甲酚紫染色大鼠的大脑。HI安慰剂组的男性伸展/收缩反应和女性翻正反射时间高于假手术组。HI安慰剂组的女性开阔野外探险次数低于假手术组。HIAIP减轻了这些行为缺陷。然而，这些反应的大小并不随hIAIP剂量的不同而变化。HIAIP以一种与改善行为结果相关的方式减少男性脑梗塞体积。将HIAIP剂量从30 mg/kg增加到90 mg/kg并没有进一步加剧HIAIP相关的脑梗塞体积的减少。我们的结论是，较大剂量的hIAIPs并没有为行为任务提供比30 mg/kg剂量更多的益处，也没有在暴露于严重HI后减少新生大鼠的脑梗塞体积。
Hypoxia–ischemia (HI)-related brain injury is an important cause of morbidity and long-standing disability in newborns. We have previously shown that human plasma-derived inter-alpha inhibitor proteins (hIAIPs) attenuate HI-related brain injury in neonatal rats. The optimal dose of hIAIPs for their neuroprotective effects and improvement in behavioral outcomes remains to be determined. We examined the efficacy of 30, 60, or 90 mg/kg of hIAIPs administered to neonatal rats after exposure to HI for 2 h. Postnatal day 7 (P7) Wistar rats were exposed to either sham-surgery or unilateral HI (right carotid artery ligation, 2 h of 8% O2) brain injury. A placebo, 30, 60, or 90 mg/kg of hIAIPs were injected intraperitoneally at 0, 24 and 48 h after HI (n = 9–10/sex). We carried out the following behavioral analyses: P8 (righting reflex), P9 (negative geotaxis) and P10 (open-field task). Rats were humanely killed on P10 and their brains were stained with cresyl violet. Male extension/contraction responses and female righting reflex times were higher in the HI placebo groups than the sham groups. Female open-field exploration was lower in the HI placebo group than the sham group. hIAIPs attenuated these behavioral deficits. However, the magnitude of the responses did not vary by hIAIP dose. hIAIPs reduced male brain infarct volumes in a manner that correlated with improved behavioral outcomes. Increasing the hIAIP dose from 30 to 90 mg/kg did not further accentuate the hIAIP-related decreases in infarct volumes. We conclude that larger doses of hIAIPs did not provide additional benefits over the 30 mg/kg dose for behavior tasks or reductions in infarct volumes in neonatal rats after exposure to severe HI.
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影响因子：
4.2
作者：
Kim, Boram;De La Monte, Suzanne;Stonestreet, Barbara S.
通讯作者：
Stonestreet, Barbara S.
影响因子：
3.4
作者：
Grewal, SS;Shepherd, JK;Dourish, CT
通讯作者：
Dourish, CT
DOI：
10.1073/pnas.0803945105
发表时间：
2008-11-25
影响因子：
11.1
作者：
Breckwoldt, Michael O.;Chen, John W.;Weissleder, Ralph
通讯作者：
Weissleder, Ralph
影响因子：
5.5
作者：
Huang, Benjamin Y.;Castillo, Mauricio
通讯作者：
Castillo, Mauricio
影响因子：
5.6
作者：
Hatayama K;Kim B;Chen X;Lim YP;Davidson JO;Bennet L;Gunn AJ;Stonestreet BS
通讯作者：
Stonestreet BS