The incidence of critical-illness-related-corticosteroid-insufficiency is associated with severity of traumatic brain injury in adult rats
The incidence of critical-illness-related-corticosteroid-insufficiency is associated with severity of traumatic brain injury in adult rats
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成年大鼠危重疾病相关皮质类固醇不足的发生率与创伤性脑损伤的严重程度相关
DOI：
10.1016/j.jns.2014.04.032
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发表时间：
2014-07-15
影响因子：
4.4
通讯作者：
Zhang, Jianning
中科院分区：
文献类型：
--
作者：
Chen, Xin;Zhao, Zilong;Zhang, Jianning
创伤性脑损伤（TBI）会导致有害的危重病相关性皮质类固醇不足（CIRCI），进而造成高死亡率和高发病率。然而，不同严重程度的TBI后CIRCI的发生率尚未完全明确。本研究旨在从机制上探讨损伤严重程度对皮质类固醇反应的影响以及在实验性可控TBI大鼠模型中CIRCI的发生情况。成年雄性Wistar大鼠被随机分为假手术组、轻度损伤组、中度损伤组和重度损伤组。采用液压冲击装置诱导TBI，冲击强度分别为12 - 1.4个大气压（轻度损伤）、2.0 - 2.2个大气压（中度损伤）和3.2 - 3.5个大气压（重度损伤）。我们首先通过电刺激试验评估皮质类固醇反应，以评估损伤严重程度对死亡率和CIRCI发生的影响。我们还研究了不同损伤组下丘脑的一系列病理变化，特别是室旁核（PVN）的变化，包括：通过TUNEL法检测细胞凋亡，通过脑含水量和伊文思蓝渗出到脑实质评估血脑屏障（BBB）通透性，以及通过CD31和克劳丁 - 5表达及透射电子显微镜评估血脑屏障完整性。我们得到了以下观察结果。首先，6.7%的轻度损伤大鼠、13.3%的中度损伤大鼠和68.8%的重度损伤大鼠发生了CIRCI，在伤后第7天发生率达到峰值。其次，TBI诱导的CIRCI与损伤严重程度密切相关。随着损伤严重程度的增加，CIRCI的发生率和死亡率均急剧上升；第三，损伤严重程度的增加会降低内皮紧密连接蛋白的表达，加重血脑屏障通透性，并加剧下丘脑室旁核随后发生的神经细胞凋亡。这些发现表明，TBI严重程度的增加会通过损害血管内皮细胞的紧密连接以及增加下丘脑室旁核的神经元凋亡，从而加重CIRCI的发生率。（C）2014爱思唯尔有限公司。保留所有权利。
Traumatic brain injury (TB!) causes deleterious critical-illness-related-corticosteroid-insufficiency (CIRCI), leading to high mortality and morbidity. However, the incidence of CIRCI following different TBI severities is not fully defined. This study was designed to investigate mechanistically the effects of injury severity on corticosteroid response and the development of CIRCI in a rat model of experimentally controlled TBI. Adult male Wistar rats were randomly assigned to sham, mild injury, moderate injury or severe injury groups. TBI was induced using a fluid percussion device at magnitudes of 12-1.4 atm (mild injury), 2.0-22 atm (moderate injury), and 3.2-3.5 atm (severe injury). We first assessed the effects of injury severity on the mortality and CIRCI occurrence using electrical stimulation test to assess corticosteroid response. We also investigated a series of pathological changes in the hypothalamus, especially in the paraventricular nuclei (PVN), among different injury group including: apoptosis detected by a TUNEL assay, blood-brain-barrier (BBB) permeability assessed by brain water content and Evans Blue extravasation into the cerebral parenchyma, and BBB integrity evaluated by CD31 and Claudin-5 expression and transmission electron microscopy. We made the following observations. First, 6.7% of mild-injured, 13.3% of moderate-injured, and 68.8% of severe-injured rats developed CIRCI, with a peak incidence on post-injury day 7. Second, TBI-induced CIRCI is closely correlated with injury severity. As the injury severity rises both the incidence of CIRCI and mortality surge; Third, increased level of injury severity reduces the expression of endothelial tight junction protein, aggravate BBB permeability and exacerbate the ensuing neural apoptosis in the PVN of hypothalamus. These findings indicate that increased severity of TBI aggravate the incidence of CIRCI by causing damage to tight junctions of vascular endothelial cells and increasing neuronal apoptosis in the PVN of hypothalamus. (C) 2014 Elsevier B.V. All rights reserved.