Rosas-Hernandez Hector, Cuevas Elvis, Escudero-Lourdes Claudia, Lantz Susan M, Sturdivant Nasya M, Imam Syed Z, Sarkar Sumit, Slikker William, Paule Merle G, Balachandran Kartik, Ali Syed F
Division of Neurotoxicology, National Center for Toxicological Research, 3900 NCTR Road, Jefferson, AR, 72079, USA.
Facultad de Ciencias Quimicas, Universidad Autonoma de San Luis Potosi, Colonia Universitaria, Av Manuel Nava 6, San Luis Potosi, 78240, Mexico.
Neurosci Lett. 2018 Apr 13;672:123-129. doi: 10.1016/j.neulet.2018.02.019. Epub 2018 Feb 16.
Traumatic brain injury (TBI) occurs when external mechanical forces induce brain damage as result of impact, penetration or rapid acceleration/deceleration that causes deformation of brain tissue. Depending on its severity, TBI can be classified as mild, moderate or severe and can lead to blood-brain barrier (BBB) dysfunction. In the present study, we evaluated the effects of uniaxial high-speed stretch (HSS) at 0, 5, 10 and 15% on a pure culture of primary rat brain endothelial cells as an in vitro model of TBI to the BBB. LDH release, viability and apoptosis analysis, expression of tight junction proteins and endothelial permeability were evaluated 24 h after a single stretch episode. HSS slightly increased cell death and apoptosis at 10 and 15%, while LDH release was increased only at 15% stretch. Occludin expression was increased at 10% stretch, while claudin-5 expression was increased at 5% stretch, which also decreased the endothelial permeability. In summary, 15% HSS induced low levels of cell death, consistent with mild TBI and very low percentages of HSS (5%) enhanced the BBB properties, promoting the formation of a stronger barrier. These data support the use of 15% HSS as valuable tool in the study of mild TBI to the BBB in vitro.
创伤性脑损伤(TBI)是指外部机械力因撞击、穿透或快速加速/减速导致脑组织变形而引起脑损伤。根据严重程度,TBI可分为轻度、中度或重度,可导致血脑屏障(BBB)功能障碍。在本研究中,我们评估了0%、5%、10%和15%的单轴高速拉伸(HSS)对原代大鼠脑内皮细胞纯培养物的影响,将其作为TBI对BBB的体外模型。在单次拉伸事件后24小时评估乳酸脱氢酶(LDH)释放、活力和凋亡分析、紧密连接蛋白的表达以及内皮通透性。10%和15%的HSS轻微增加细胞死亡和凋亡,而仅在15%拉伸时LDH释放增加。10%拉伸时闭合蛋白表达增加,5%拉伸时claudin-5表达增加,这也降低了内皮通透性。总之,15%的HSS诱导低水平的细胞死亡,与轻度TBI一致,极低百分比的HSS(5%)增强了BBB特性,促进形成更强的屏障。这些数据支持将15%的HSS用作体外研究轻度TBI对BBB的有价值工具。