Lovastatin improves histological and functional outcomes and reduces inflammation after experimental traumatic brain injury
Lovastatin improves histological and functional outcomes and reduces inflammation after experimental traumatic brain injury
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DOI：
10.1016/j.lfs.2007.05.023
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发表时间：
2007-07-04
期刊：
影响因子：
6.1
通讯作者：
Wang, Jia-Yi
中科院分区：
文献类型：
--
作者：
Chen, Szu-Fu;Hung, Tai-Ho;Wang, Jia-Yi
创伤性脑损伤(TBI)触发一系列复杂的炎症反应，导致继发性损伤。他汀类药物已显示出对脑损伤的神经保护作用，但其潜在机制尚不清楚。这项研究评估了洛伐他汀对控制性皮质撞击(CCI)损伤大鼠模型的影响。我们的两个假设是，预先服用洛伐他汀可以减少功能缺陷和脑解剖损伤的程度，而且洛伐他汀可以减弱促炎细胞因子的水平。给大鼠注射洛伐他汀(4 mg/kg)或赋形剂5d后行CCI。通过旋转棒和粘合剂去除试验评估神经状态。用甲酚紫和荧光素B(FJB)组织化学方法检测挫伤体积和神经元变性。用实时定量逆转录聚合酶链式反应、酶联免疫吸附试验和免疫组织化学方法检测肿瘤坏死因子-α(TNF-α)和白介素1-β(IL-1β)的mRNA和蛋白水平。洛伐他汀在伤后第7天前显著改善了旋转棒和粘合剂去除试验的表现。洛伐他汀还显著减少了伤后4天的挫伤体积(20%)和FJB阳性变性神经元的数量(35%)。这些变化与肿瘤坏死因子-α和白介素I-β水平的显著下降有关。伤后6天和4天，挫伤部位的mRNA和蛋白表达水平明显升高。我们的结果表明，洛伐他汀预给药改善了功能结果，减轻了脑损伤程度，并伴随着组织中肿瘤坏死因子-α和白介素1-β的mRNA和蛋白水平的降低。这些发现表明，洛伐他汀的保护机制可能部分归因于抑制炎症反应。(C)2007 Elsevier Inc.保留所有权利。
Traumatic brain injury (TBI) triggers a complex sequence of inflammatory responses that contribute to secondary injury. Statins have demonstrated neuroprotective effects against brain injury, but the underlying mechanisms remain unclear. This study evaluated the effects of lovastatin on a rat model of controlled cortical impact (CCI) injury. Our two hypotheses were that pre-administration of lovastatin would reduce functional deficits and extent of anatomical brain damage and that lovastatin would attenuate levels of pro-inflammatory cytokines. Rats were injected with lovastatin (4 mg/kg) or vehicle for 5 days and subjected to CCI. Neurological status was evaluated using rotarod and adhesive removal tests. Contusion volume and neuronal degeneration were examined using cresyl violet and FluoroJade B (FJB) histochemistry. Levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin- 1 beta (IL- 1 beta) mRNA and protein were assessed by real-time quantitative reverse transcriptase polymerase chain reaction, enzyme-linked immunosorbent assay, and immunohistochemistry. Lovastatin significantly improved performance on both the rotarod and adhesive removal tests before post-injury day 7. Lovastatin also significantly reduced contusion volume (20%) and number of FJB-positive degenerating neurons (35%) at 4 days. These changes were associated with a significant decrease in levels of TNF-a and IL-I beta. mRNA and protein at the contusion site at 6 It and 4 days, respectively. Our results show that pre-administration of lovastatin improved functional outcomes and reduced extent of brain damage, with a concomitant decrease in tissue levels of TNF-alpha and IL- 1 beta mRNA and protein. These findings suggest that lovastatin's protective mechanisms may be partly attributed to a dampening of the inflammatory response. (c) 2007 Elsevier Inc. All rights reserved.