title: Association of Long-Term Atorvastatin with Escalated Stroke-Induced Neuroinflammation in Rats.
abstract: Statins are widely used in high-risk patients to reduce the stroke incidence. However, little has been investigated about the impact of chronic pretreatment with statins on cerebral ischemic insult following defined arterial occlusion. To address this in experimental rats, in the present work, atorvastatin was orally dosed for 1 month to evaluate the outcomes of the subsequent occlusive stroke induced by middle cerebral artery occlusion (MCAO). Our data was suggestive of potential escalating impact of chronic atorvastatin (Atv; 10 mg/kg) on neurological function, but not infarct volume. According to our immunoblotting data, such escalations were consistent with the prominent rise in TNF-α and IL-6 which paralleled with augmented Bax/Bcl2 ratio and Caspase-9 activation; however, these were not enough to worsen acute neurodegeneration determined by Fluoro Jade B staining. Noteworthy, such deteriorating effects were also partly detected in non-ischemic animals. Conclusively, our data are indicative of cerebral proinflammatory effects of chronic Atv which might overwhelm the beneficial pliotropic of the drug and predispose animals' brain to ischemic insult. Further studies on different statins with discrete pharmacokinetic properties are highly suggested to precisely explore stroke outcomes following long term prophylactic treatment particularly in primates.
authors.affiliation: Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Leila
authors.initials: L
authors.lastname: Simani
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, P.O. BOX 19615-1178, Tehran, Iran.
authors.forename: Nima
authors.initials: N
authors.lastname: Naderi
authors.affiliation: Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Fariba
authors.initials: F
authors.lastname: Khodagholi
authors.affiliation: Department of Neurology, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Masoud
authors.initials: M
authors.lastname: Mehrpour
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, P.O. BOX 19615-1178, Tehran, Iran. sanaznasoohi@sbmu.ac.ir.
authors.forename: Sanaz
authors.initials: S
authors.lastname: Nasoohi
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D000069059:Atorvastatin / Q000008:administration & dosage / Q000009:adverse effects*; D053453:Caspase 9 / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism*; D007249:Inflammation / Q000209:etiology; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000924:Anticholesteremic Agents; D015850:Interleukin-6; D019253:Proto-Oncogene Proteins c-bcl-2; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; D000069059:Atorvastatin; D053453:Caspase 9
keywords: Atorvastatin; Cerebral ischemia; Neuroinflammation