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.
Abrahamson
Eric E
EE
Department of Neurology, Brain Trauma Research Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Ikonomovic
Milos D
MD
Dixon
C Edward
CE
DeKosky
Steven T
ST
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