Stress-dose hydrocortisone reduces critical illness-related corticosteroid insufficiency associated with severe traumatic brain injury in rats.
Stress-dose hydrocortisone reduces critical illness-related corticosteroid insufficiency associated with severe traumatic brain injury in rats.
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应激剂量氢化可的松可减少与大鼠严重创伤性脑损伤相关的危重疾病相关皮质类固醇不足
DOI：
10.1186/cc13067
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发表时间：
2013-10-16
期刊：
影响因子：
--
通讯作者：
Zhang J
中科院分区：
文献类型：
--
作者：
Chen X;Zhao Z;Chai Y;Luo L;Jiang R;Dong J;Zhang J
严重创伤性脑损伤（TBI）中危重病相关皮质类固醇不足（CIRCI）的范围尚未完全确定，迄今为止还没有有效的治疗TBI诱导的CIRCI的方法。尽管越来越多的人对使用应激剂量的氢化可的松作为CIRCI的潜在治疗方法感兴趣，但关于其在严重TBI后的益处的数据仍然很少。本研究旨在研究应激剂量氢化可的松对大鼠严重创伤性脑损伤模型CIRCI发展和神经功能结局的影响。大鼠遭受3.2-3.5个大气压的侧向液压冲击损伤。然后在损伤后7天，每天用应激剂量氢化可的松（HC，3 mg/kg/d，持续5天，第6天1.5 mg/kg，第7天0.75 mg）、低剂量甲基强的松龙（MP，1 mg/kg/d，持续5天，第6天0.5 mg/kg，第7天0.25 mg）或对照盐水溶液腹膜内治疗这些大鼠。我们研究了应激剂量HC对死亡率、CIRCI发生率和神经功能缺损的影响，使用电刺激试验评估皮质类固醇反应和改良神经系统严重程度评分（mNSS）。我们还研究了应激剂量HC或低剂量MP给药后下丘脑，特别是室旁核（PVN）的病理变化，包括TUNEL法检测细胞凋亡，通过脑含水量和Evans蓝外渗到脑实质评估血脑屏障（BBB）通透性，以及通过CD 31和claudin-5表达评估BBB完整性。我们提出了以下意见。首先，70%的损伤大鼠发生CIRCI，在损伤后第7天发病率达到高峰。TBI相关的CIRCI与死亡率增加和神经功能恢复延迟密切相关。其次，在损伤后给药的前14天内，损伤后给予应激剂量的HC，而不是MP或盐水，增加了皮质类固醇反应，预防了CIRCI，降低了死亡率，并改善了神经功能。第三，这些有益的作用是密切相关的血管功能的保护，在存活的内皮细胞的紧密连接，减少神经细胞凋亡的下丘脑室旁核。我们的研究结果表明，损伤后给予应激剂量的HC，而不是MP，可以降低CIRCI并改善神经恢复。这些改善与减少对血管内皮细胞紧密连接的损伤和阻断下丘脑PVN中的神经元凋亡有关。
The spectrum of critical illness-related corticosteroid insufficiency (CIRCI) in severe traumatic brain injury (TBI) is not fully defined and no effective treatments for TBI-induced CIRCI are available to date. Despite growing interest in the use of stress-dose hydrocortisone as a potential therapy for CIRCI, there remains a paucity of data regarding its benefits following severe TBI. This study was designed to investigate the effects of stress-dose hydrocortisone on CIRCI development and neurological outcomes in a rat model of severe traumatic brain injury. Rats were subjected to lateral fluid percussion injury of 3.2-3.5 atmosphere. These rats were then treated with either a stress-dose hydrocortisone (HC, 3 mg/kg/d for 5 days, 1.5 mg/kg on day 6, and 0.75 mg on day 7), a low-dose methylprednisolone (MP, 1 mg/kg/d for 5 days, 0.5 mg/kg on day 6, and 0.25 mg on day 7) or control saline solution intraperitoneally daily for 7 days after injury. We investigated the effects of stress-dose HC on the mortality, CIRCI occurrence, and neurological deficits using an electrical stimulation test to assess corticosteroid response and modified neurological severity score (mNSS). We also studied pathological changes in the hypothalamus, especially in the paraventricular nuclei (PVN), after stress-dose HC or a low dose of MP was administered, 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. We made the following observations. First, 70% injured rats developed CIRCI, with a peak incidence on post-injury day 7. The TBI-associated CIRCI was closely correlated with an increased mortality and delayed neurological recovery. Second, post-injury administration of stress-dose HC, but not MP or saline increased corticosteroid response, prevented CIRCI, reduced mortality, and improved neurological function during the first 14 days post injury dosing. Thirdly, these beneficial effects were closely related to improved vascular function by the preservation of tight junctions in surviving endothelial cells, and reduced neural apoptosis in the PVN of hypothalamus. Our findings indicate that post-injury administration of stress-dose HC, but not MP reduces CIRCI and improves neurological recovery. These improvements are associated with reducing the damage to the tight junction of vascular endothelial cells and blocking neuronal apoptosis in the PVN of the hypothalamus.
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DOI：
10.1186/cc11871
发表时间：
2012-11-21
期刊：
Critical care (London, England)
影响因子：
--
作者：
Jung B;Clavieras N;Nougaret S;Molinari N;Roquilly A;Cisse M;Carr J;Chanques G;Asehnoune K;Jaber S
通讯作者：
Jaber S
DOI：
10.1073/pnas.95.26.15635
发表时间：
1998-12-22
影响因子：
11.1
作者：
Ji, RR;Schlaepfer, TE;Rupp, F
通讯作者：
Rupp, F
DOI：
10.1083/jcb.119.3.493
发表时间：
1992-11
期刊：
The Journal of cell biology
影响因子：
--
作者：
Gavrieli Y;Sherman Y;Ben-Sasson SA
通讯作者：
Ben-Sasson SA
影响因子：
34.7
作者：
Krugers, Harmen J.;Hoogenraad, Casper C.;Groc, Laurent
通讯作者：
Groc, Laurent
影响因子：
4.2
作者：
Chen, Xin;Zhang, Ke-Li;Zhang, Jian-Ning
通讯作者：
Zhang, Jian-Ning