Atorvastatin protects rat brains against permanent focal ischemia and downregulates HMGB1, HMGB1 receptors (RAGE and TLR4), NF-κB expression

被引:108
作者
Wang, Lina [1 ]
Zhang, Xiangjian [1 ]
Liu, Lingling [1 ]
Yang, Rui [1 ]
Cui, Lili [1 ]
Li, Min [1 ]
机构
[1] Hebei Med Univ, Hosp 2, Dept Neurol, Shijiazhuang 050000, Hebei, Peoples R China
关键词
Cerebral ischemia; High-mobility group box 1; Atorvastatin; Neuroprotection; CEREBRAL-ARTERY OCCLUSION; STROKE; ACTIVATION;
D O I
10.1016/j.neulet.2010.01.030
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Inflammatory processes play a key, mainly detrimental role in the pathophysiology of ischemic stroke. Currently, HMGB1-induced NF-kappa B activation pathway has been recognized as a key contributor to the proinflammatory response. It has been proved that chronic administration and pre-treatment with statins could protect brain tissue against ischemic injury. However, little is known about the effects of statins in the acute phase after cerebral ischemia. Thus, this study investigated the atorvastatin's protective role and the underlying mechanisms in cerebral ischemia. After middle cerebral artery occlusion (MCAO), atorvastatin was administered immediately. WE found that atorvastatin dramatically improved neurological deficits, reduced brain water contents and infarct sizes at 24 h after stroke. Moreover, the over-expression of HMGB1, TLR4 and NF-kappa B induced by ischemia was significantly attenuated by atorvastatin. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:152 / 156
页数:5
相关论文
共 27 条
[1]   Nogo-A expression after focal ischemic stroke in the adult rat [J].
Cheatwood, Joseph L. ;
Emerick, April J. ;
Schwab, Martin E. ;
Kartje, Gwendolyn L. .
STROKE, 2008, 39 (07) :2091-2098
[2]   Drug-induced neuroprotection from global ischemia is associated with prevention of persistent but not transient activation of nuclear factor-κB in rats [J].
Clemens, JA ;
Stephenson, DT ;
Yin, TG ;
Smalstig, EB ;
Panetta, JA ;
Little, SP .
STROKE, 1998, 29 (03) :677-682
[3]   Global cerebral ischemia activates nuclear factor-kappa B prior to evidence of DNA fragmentation [J].
Clemens, JA ;
Stephenson, DT ;
Dixon, EP ;
Smalstig, EB ;
Mincy, RE ;
Rash, KS ;
Little, SP .
MOLECULAR BRAIN RESEARCH, 1997, 48 (02) :187-196
[4]  
Dirnagl U, 2004, E SCHERING RES FDN W, V47, P87
[5]   Stroke [J].
Donnan, Geoffrey A. ;
Fisher, Marc ;
Macleod, Malcolm ;
Davis, Stephen M. .
LANCET, 2008, 371 (9624) :1612-1623
[6]   Amphoterin as an extracellular regulator of cell motility: from discovery to disease [J].
Huttunen, HJ ;
Rauvala, H .
JOURNAL OF INTERNAL MEDICINE, 2004, 255 (03) :351-366
[7]   Antioxidant nutrients and hypoxia/ischemia brain injury in rodents [J].
Ikeda, K ;
Negishi, H ;
Yamori, Y .
TOXICOLOGY, 2003, 189 (1-2) :55-61
[8]   Lipophilic HMG-CoA reductase inhibitor has an anti-inflammatory effect -: Reduction of MRNA levels for interleukin-1β, interleukin-6, cyclooxygenase-2, and p22phox by regulation of peroxisome proliferator-activated receptor α (PPARα) in primary endothelial cells [J].
Inoue, I ;
Goto, S ;
Mizotani, K ;
Awata, T ;
Mastunaga, T ;
Kawai, S ;
Nakajima, T ;
Hokari, S ;
Komoda, T ;
Katayama, S .
LIFE SCIENCES, 2000, 67 (08) :863-876
[9]   Atorvastatin upregulates type III nitric oxide synthase in thrombocytes, decreases platelet activation, and protects from cerebral ischemia in normocholesterolemic mice [J].
Laufs, U ;
Gertz, K ;
Huang, P ;
Nickenig, G ;
Böhm, M ;
Dirnagl, U ;
Endres, M .
STROKE, 2000, 31 (10) :2442-2448
[10]   Free radical pathways in CNS injury [J].
Lewén, A ;
Matz, P ;
Chan, PH .
JOURNAL OF NEUROTRAUMA, 2000, 17 (10) :871-890