title: Simvastatin and atorvastatin improve behavioral outcome, reduce hippocampal degeneration, and improve cerebral blood flow after experimental traumatic brain injury.
abstract: The treatment of traumatic brain injury (TBI) remains limited, and aside from surgical hematoma evacuation, clinical management is largely supportive and directed toward management of cerebral edema and intracranial hypertension. Secondary neuronal injury caused by ischemia and the development of cerebral edema may occur in the subacute phase, with intracranial pressures often peaking in the first several days following injury. Because inflammation contributes significantly to the pathophysiology of cerebral ischemia and endothelial dysfunction underlies the development of cerebral edema, therapeutic strategies that target the post-traumatic inflammatory cascade and reduce endothelial dysfunction hold enormous potential to improve clinical outcomes after TBI. Statins inhibit inflammation by suppressing inflammatory cytokine release, and by interfering with multiple steps of leukocyte recruitment and migration into the CNS. In this study, we demonstrate that treatment with atorvastatin and simvastatin markedly reduced functional neurological deficits after traumatic brain injury in mice. These effects were accompanied by histological reduction in degenerating hippocampal neurons and suppression of inflammatory cytokine mRNA expression in brain parenchyma. Furthermore, statin treatment improved cerebral hemodynamics following head injury. Thus, the administration of statins may represent a viable therapeutic strategy in the acute treatment of closed head injury.
authors.affiliation: Department of Medicine, Division of Neurology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Haichen
authors.initials: H
authors.lastname: Wang
authors.forename: John R
authors.initials: JR
authors.lastname: Lynch
authors.forename: Pingping
authors.initials: P
authors.lastname: Song
authors.forename: Hyuk-Jun
authors.initials: HJ
authors.lastname: Yang
authors.forename: Robert B
authors.initials: RB
authors.lastname: Yates
authors.forename: Brian
authors.initials: B
authors.lastname: Mace
authors.forename: David S
authors.initials: DS
authors.lastname: Warner
authors.forename: John R
authors.initials: JR
authors.lastname: Guyton
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Laskowitz
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D000069059:Atorvastatin; D001929:Brain Edema / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D001930:Brain Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects* / Q000502:physiology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000502:physiology; D003072:Cognition Disorders / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D016207:Cytokines / Q000235:genetics; D004195:Disease Models, Animal; D004660:Encephalitis / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006538:Heptanoic Acids / Q000494:pharmacology / Q000627:therapeutic use; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D019821:Simvastatin / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D012333:RNA, Messenger; D000069059:Atorvastatin; D019821:Simvastatin