title: Lipid-lowering drugs prevent neurovascular and cognitive consequences of cardiopulmonary bypass.
abstract: Inflammatory injury and hypoperfusion following cardiopulmonary bypass (CPB) are associated with potential brain injury in relationship between CPB, memory impairment, changes in cerebral vascular reactivity and both systemic and cerebral inflammatory reaction. The objective of this study was to assess the preventive effect of a pretreatment with simvastatin or fenofibrate on neurovascular and cognitive consequences of CPB. Male Sprague-Dawley rats were treated by control diet, simvastatin 10 mg/kg/day or fenofibrate 200 mg/kg/day for 14 days before CPB surgery and were sacrificed immediately after surgery or 24h later. Cognitive function, vascular reactivity, neuronal counts in CA1 and CA3 hippocampal regions, and inflammatory markers were assessed. CPB induced memory impairment and endothelial dysfunction 24h after surgery associated with neuronal loss. Neuronal loss was reduced by simvastatin or fenofibrate treatment in parallel to memory alteration prevention. Pretreatment by simvastatin and fenofibrate prevented CPB-induced endothelial dysfunction. CPB led to early and marked release of TNFα and overexpression of ICAM-1. Both inflammatory marker expression was decreased in the pretreated groups by lipid-lowering drugs. In a rat model of CPB, we demonstrated that simvastatin and fenofibrate protected against CPB-induced endothelial dysfunction, cerebral and systemic inflammation in parallel to memory impairment prevention.
authors.affiliation: Inserm, CHU Lille, U1171, Degenerative & Vascular Cognitive Disorders, Univ. Lille, F-59000 Lille, France.
authors.forename: Thavarak
authors.initials: T
authors.lastname: Ouk
authors.affiliation: Inserm, CHU Lille, U1171, Degenerative & Vascular Cognitive Disorders, Univ. Lille, F-59000 Lille, France; Service de Chirurgie Cardiovasculaire, Hôpital cardiologique; Centre Hospitalier Universitaire de Lille, F-59000 Lille, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Amr
authors.affiliation: Inserm, CHU Lille, U1171, Degenerative & Vascular Cognitive Disorders, Univ. Lille, F-59000 Lille, France; Service de Chirurgie Cardiovasculaire, Hôpital cardiologique; Centre Hospitalier Universitaire de Lille, F-59000 Lille, France.
authors.forename: Richard
authors.initials: R
authors.lastname: Azzaoui
authors.affiliation: Inserm, CHU Lille, U1171, Degenerative & Vascular Cognitive Disorders, Univ. Lille, F-59000 Lille, France.
authors.forename: Laëtitia
authors.initials: L
authors.lastname: Delassus
authors.affiliation: Inserm, CHU Lille, U1171, Degenerative & Vascular Cognitive Disorders, Univ. Lille, F-59000 Lille, France; Service de Chirurgie Cardiovasculaire, Hôpital cardiologique; Centre Hospitalier Universitaire de Lille, F-59000 Lille, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Fossaert
authors.affiliation: Inserm, CHU Lille, Institut Pasteur de Lille, U1011-EGID, Univ. Lille, F-59000 Lille, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Tailleux
authors.affiliation: Inserm, CHU Lille, U1171, Degenerative & Vascular Cognitive Disorders, Univ. Lille, F-59000 Lille, France.
authors.forename: Régis
authors.initials: R
authors.lastname: Bordet
authors.affiliation: Inserm, CHU Lille, U1171, Degenerative & Vascular Cognitive Disorders, Univ. Lille, F-59000 Lille, France; Service de Chirurgie Cardiovasculaire, Hôpital cardiologique; Centre Hospitalier Universitaire de Lille, F-59000 Lille, France. Electronic address: thomas.modine@chru-lille.fr.
authors.forename: Thomas
authors.initials: T
authors.lastname: Modine
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D002561:Cerebrovascular Disorders / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D003072:Cognition Disorders / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D004730:Endothelium, Vascular / Q000187:drug effects; D011345:Fenofibrate / Q000008:administration & dosage / Q000627:therapeutic use; D006439:Hemodynamics / Q000187:drug effects; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D008055:Lipids / Q000097:blood; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D017207:Rats, Sprague-Dawley; D019821:Simvastatin / Q000008:administration & dosage / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014664:Vasodilation / Q000187:drug effects
chemical_list: D000960:Hypolipidemic Agents; D008055:Lipids; D018696:Neuroprotective Agents; D014409:Tumor Necrosis Factor-alpha; D019821:Simvastatin; D011345:Fenofibrate
keywords: Cardiopulmonary bypass; Cerebrovascular diseases; Endothelium; Inflammation; Lipid-lowering drugs