Atorvastatin attenuates NF-kappaB activation in trigeminal nucleus caudalis in a rat model of migraine.
Nitroglycerin-induced NF-kappaB activation in trigeminal nucleus caudalis is believed to be partly involved in the pathogenesis of migraine. Atorvastatin, an inhibitor of HMG-CoA reductase, is thought to have pleiotropic effects in various neurologic diseases. Moreover, there are several lines of evidences that atorvastatin inhibits NF-kappaB activation in peripheral blood mononuclear cells. Thus, this study aims to explore whether atorvastatin attenuates NF-kappaB activation in trigeminal nucleus caudalis in a nitroglycerin-induced migraine model. A significant increase in nuclear content of p65, an indicator of NF-kappaB activation, was detected in trigeminal nucleus caudalis in rats following injection with nitroglycerin. However, the nitroglycerin-induced NF-kappaB activation in trigeminal nucleus caudalis was attenuated by pretreatment with atorvastatin in a dose-dependent fashion. These results suggest that atorvastatin may be a novel and promising candidate for future treatment or prophylaxis of migraine via attenuating activation of NF-kappaB in trigeminal nucleus caudalis.
Yin
Zhao
Z
Department of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, No. 58 Zhongshan Road 2, Guangzhou 510080, China. megayin@126.com
Fang
Yannan
Y
Ren
Li
L
Wang
Xiaojuan
X
Zhang
Aiwu
A
Lin
Jianwen
J
Li
Xianliang
X
D000704:Analysis of Variance; D000818:Animals; D000069059:Atorvastatin; D015153:Blotting, Western; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005455:Fluorescent Antibody Technique; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008881:Migraine Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D005996:Nitroglycerin; D029543:Nucleocytoplasmic Transport Proteins / Q000378:metabolism; D011758:Pyrroles / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014275:Trigeminal Caudal Nucleus / Q000187:drug effects* / Q000378:metabolism
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D016328:NF-kappa B; D009363:Neoplasm Proteins; D029543:Nucleocytoplasmic Transport Proteins; D011758:Pyrroles; C063447:p65 oncofetal mRNA transport protein, rat; D000069059:Atorvastatin; D005996:Nitroglycerin