Novel Injury Scoring Tool for Assessing Brain Injury following Neonatal Hypoxia-Ischemia in Mice.
Novel Injury Scoring Tool for Assessing Brain Injury following Neonatal Hypoxia-Ischemia in Mice.
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DOI：
10.1159/000525244
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发表时间：
2022
影响因子：
2.9
通讯作者：
Cengiz, Pelin
中科院分区：
文献类型：
--
作者：
Ozaydin, Burak;Bicki, Ela;Taparli, Onur E.;Sheikh, Temour Z.;Schmidt, Danielle K.;Yapici, Sefer;Hackett, Margarett B.;Karahan-Keles, Nida;Eickhoff, Jens C.;Corcoran, Karson;Lagoa-Miguel, Claudia;Guerrero Gonzalez, Jose;Dean III, Douglas C.;Sousa, Andre M. M.;Ferrazzano, Peter A.;Levine, Jon E.;Cengiz, Pelin
关键词：
研究对象之间缺氧缺血(HI)所致脑损伤严重程度的差异是发育性脑损伤研究中的一大挑战。我们的实验室开发了一种新的损伤评分工具，该工具基于我们在海马区提取过程中的大体病理观察。HI后大鼠海马区评分为0~6分，0分为无损伤，6分为重度损伤。将暴露于假手术的海马区归为无损伤组。我们通过T2加权MRI分析新生小鼠暴露于Vannucci的新生HI啮齿动物模型后的海马/半球组织丢失百分比和细胞存活/死亡标记，验证了损伤评分工具。此外，我们还分离了海马核，并量化了优质核团的百分比，为我们新的损伤评分工具的应用提供了一个例子。我们的新损伤评分与海马区和半球组织损失率、细胞存活/死亡标记物和优质细胞核百分比显著相关。Caspase-3和多聚(ADP-核糖)聚合酶-1(PARP1)参与了新生儿缺氧缺血性脑病不同的细胞死亡途径。另一个基因，Sirtuin1(SIRT1)，已被证明具有神经保护和抗细胞凋亡的特性。为了评估损伤程度与细胞存活/死亡相关基因之间的相关性，我们利用RT-qPCR技术分析了HI和Sham手术后3天海马区caspase-3、PARP1和SIRT1mRNA的表达。HI后同侧(IL)海马区caspase-3和SIRT1mRNA的表达显著高于假手术侧，且男女均与新损伤评分呈正相关。我们发现IL海马半胱氨酸氨基转移酶-3基因表达的性别差异具有统计学意义，男性和女性之间的损伤评分相似，女性的表达更高。
The variability of severity in hypoxia ischemia (HI) induced brain injury among research subjects is a major challenge in developmental brain injury research. Our laboratory developed a novel injury scoring tool based on our gross pathological observations during hippocampal extraction. The hippocampi received scores of 0–6 with 0 being no injury and 6 being severe injury post-HI. The hippocampi exposed to sham surgery were grouped as having no injury. We have validated the injury scoring tool with T2-weighted MRI analysis of percent hippocampal/hemispheric tissue loss and cell survival/death markers after exposing the neonatal mice to Vannucci’s rodent model of neonatal HI. In addition, we have isolated hippocampal nuclei and quantified the percent good quality nuclei to provide an example of utilization of our novel injury scoring tool. Our novel injury scores correlated significantly with percent hippocampal and hemispheric tissue loss, cell survival/death markers, and percent good quality nuclei. Caspase-3 and Poly (ADP-ribose) polymerase-1 (PARP1) have been implicated in different cell death pathways in response to neonatal HI. Another gene, sirtuin1 (SIRT1), has been demonstrated to have neuroprotective and anti-apoptotic properties. To assess the correlation between the severity of injury and genes involved in cell survival/death, we analyzed caspase-3, PARP1, and SIRT1 mRNA expressions in hippocampi 3 days post-HI and sham surgery, using RT-qPCR. The ipsilateral (IL) hippocampal caspase-3 and SIRT1 mRNA expressions post-HI were significantly higher than sham IL hippocampi, and positively correlated with the novel injury scores in both males and females. We detected a statistically significant sex difference in IL hippocampal caspase-3 mRNA expression with comparable injury scores between males and females with higher expression in females.
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影响因子：
8.3
作者：
Liu F;Li Z;Li J;Siegel C;Yuan R;McCullough LD
通讯作者：
McCullough LD
在新生儿缺氧 - 缺血症的大鼠模型中，使用体温过低和红细胞生成素组合疗法的影响。
影响因子：
3.6
作者：
Fang, Annie Y.;Gonzalez, Fernando F.;Sheldon, R. Ann;Ferriero, Donna M.
通讯作者：
Ferriero, Donna M.
影响因子：
14.8
作者：
Beaudoin, Gerard M. J., III;Lee, Seung-Hye;Arikkath, Jyothi
通讯作者：
Arikkath, Jyothi
影响因子：
2.9
作者：
Hill, C. A.;Alexander, M. L.;Fitch, R. H.
通讯作者：
Fitch, R. H.
影响因子：
2.9
作者：
Askalan, Rand;Gabarin, Nadia;Yager, Jerome Y.
通讯作者：
Yager, Jerome Y.