Simvastatin therapy prevents brain trauma-induced increases in beta-amyloid peptide levels.
Elevations in beta-amyloid peptide (A beta) levels after traumatic brain injury (TBI) may confer risk for developing Alzheimer's disease in head trauma patients. We investigated the effects of simvastatin, a 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor, on hippocampal A beta burden in a clinically relevant head injury/intervention model using mice expressing human A beta. Simvastatin therapy blunted TBI-induced increases in A beta, reduced hippocampal tissue damage and microglial activation, and improved behavioral outcome. The ability of statins to reduce post-injury A beta load and ameliorate pathological sequelae of brain injury makes them potentially effective in reducing the risk of developing Alzheimer's disease in TBI patients.
Department of Neurology, Brain Trauma Research Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Eric E
EE
Abrahamson
Milos D
MD
Ikonomovic
C Edward
CE
Dixon
Steven T
ST
DeKosky
D000544:Alzheimer Disease / Q000517:prevention & control*; D016229:Amyloid beta-Peptides / Q000032:analysis* / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001930:Brain Injuries / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D006624:Hippocampus / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D004856:Postural Balance / Q000187:drug effects; D012307:Risk Factors; D019821:Simvastatin / Q000494:pharmacology / Q000627:therapeutic use*; D014018:Tissue Distribution / Q000187:drug effects
D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D019821:Simvastatin