Atorvastatin protects rat brains against permanent focal ischemia and downregulates HMGB1, HMGB1 receptors (RAGE and TLR4), NF-kappaB expression.
Inflammatory processes play a key, mainly detrimental role in the pathophysiology of ischemic stroke. Currently, HMGB1-induced NF-kappaB 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 24h after stroke. Moreover, the over-expression of HMGB1, RAGE, TLR4 and NF-kappaB induced by ischemia was significantly attenuated by atorvastatin.
Wang
Lina
L
Department of Neurology, Second Hospital of Hebei Medical University, No. 251 Hepingxi Road, Shijiazhuang, Hebei 050000, China.
Zhang
Xiangjian
X
Liu
Lingling
L
Yang
Rui
R
Cui
Lili
L
Li
Min
M
D000818:Animals; D000069059:Atorvastatin; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001929:Brain Edema / Q000517:prevention & control; D020520:Brain Infarction / Q000473:pathology / Q000517:prevention & control; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015536:Down-Regulation; D024243:HMGB1 Protein / Q000096:biosynthesis*; D006538:Heptanoic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D016328:NF-kappa B / Q000096:biosynthesis*; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000096:biosynthesis*; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis*
D024243:HMGB1 Protein; C104200:Hbp1 protein, rat; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D016328:NF-kappa B; D018696:Neuroprotective Agents; D011758:Pyrroles; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D000069059:Atorvastatin