Early inflammatory mediator gene expression in two models of traumatic brain injury: ex vivo cortical slice in mice and in vivo cortical impact in piglets.
Early inflammatory mediator gene expression in two models of traumatic brain injury: ex vivo cortical slice in mice and in vivo cortical impact in piglets.
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DOI：
10.1186/s12974-015-0298-4
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发表时间：
2015-04-18
影响因子：
9.3
通讯作者：
Hickey WF
中科院分区：
文献类型：
--
作者：
Graber DJ;Costine BA;Hickey WF
创伤性脑损伤（TBI）后最初24小时内的免疫反应可能是限制继发性神经元损伤的关键治疗间隔，继发性神经元损伤受炎症介质表达增强的影响。为了进一步了解早期损伤反应，我们在两种不同的哺乳动物模型中通过实时qPCR检查了几种炎症基因的表达与损伤时间或距离的函数关系：离体小鼠皮质切片损伤系统和体内小鼠脑损伤模型。在小鼠皮层切片中，白细胞介素-1 β（IL-1 β）、肿瘤坏死因子-α（TNF-α）、趋化因子配体2（CCL 2）、3（CCL 3）、4（CCL 4）和胰高血糖素-内过氧化物合酶2（PTGS 2）mRNA在损伤后5小时内增加。在24 h切片中，趋化因子和PTGS 2 mRNA仍然升高，而IL-1 β和TNF-α表达从早期峰值水平下降。1月龄仔猪皮层损伤后24 h，损伤核心区和半影区CCL2 mRNA表达显著增加。PTGS 2、IL-1 β和TNF-α的表达在仔猪中是可变的。这些在体外和大型动物模型的皮质损伤扩展了我们的理解的免疫反应的早期时间和传播，并可以作为临床前系统，以促进TBI的治疗药物的发现，旨在调节炎症介质的表达。
The immunological response during the first 24 hours after traumatic brain injury (TBI) may be a critical therapeutic interval for limiting the secondary neuronal damage that is influenced by enhanced inflammatory mediator expression. To gain further insight of the early injury response, we examined the expression of several inflammatory genes by real-time qPCR as a function of time or distance from injury in two distinct mammalian models: an ex vivo mouse cortical slice injury system and an in vivo piglet model of brain injury. Interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), chemokine ligands 2 (CCL2), 3 (CCL3), 4 (CCL4), and prostaglandin-endoperoxide synthase 2 (PTGS2) mRNAs increased within 5 h after injury in mouse cortical slices. Chemokine and PTGS2 mRNAs remained elevated in slices at 24 h, whereas IL-1β and TNF-α expressions decreased from earlier peak levels. At 24 h after cortical injury in 1-month-old piglets, the expression of CCL2 mRNA was significantly increased in the lesion core and in the penumbra region. The expression of PTGS2, IL-1β, and TNF-α was variable among the piglets. These in vitro and large animal models of cortical injury expand our understanding of the early timing and spread of the immunological response and can serve as preclinical systems to facilitate the discovery of therapeutic agents for TBI aimed at regulating inflammatory mediator expression.
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影响因子：
6.3
作者：
Helmy, Adel;Guilfoyle, Mathew R.;Hutchinson, Peter J.
通讯作者：
Hutchinson, Peter J.
影响因子：
4.1
作者：
Duhaime, AC;Margulies, SS;Raghupathi, R
通讯作者：
Raghupathi, R
影响因子：
--
作者：
Schmidt, OI;Heyde, CE;Stahel, PF
通讯作者：
Stahel, PF
影响因子：
2.5
作者：
DOBBING, J;SANDS, J
通讯作者：
SANDS, J
DOI：
10.1016/j.nurt.2010.07.002
发表时间：
2010-10
期刊：
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics
影响因子：
--
作者：
Loane DJ;Byrnes KR
通讯作者：
Byrnes KR