title: A novel therapeutic derived from apolipoprotein E reduces brain inflammation and improves outcome after closed head injury.
abstract: Although apolipoprotein E4 (APOE4) was initially identified as a susceptibility gene for the development of Alzheimer's disease, the presence of the APOE4 allele is also associated with poor outcome after acute brain injury. One mechanism by which apoE may influence neurological outcome is by downregulating the neuroinflammatory response. Because it does not readily cross the blood-brain barrier, the apoE holoprotein has limited therapeutic potential. We demonstrate that a single intravenous injection of a small peptide derived from the apoE receptor binding region crosses the blood-brain barrier and significantly improves histological and functional outcomes after traumatic brain injury (TBI). The development of an apoE-based intervention represents a novel therapeutic strategy in the management of acute brain injury.
authors.affiliation: The Multidisciplinary Neuroprotection Laboratories, Duke University Medical Center, Durham, NC 27710, USA. lynch004@duke.edu
authors.forename: John R
authors.initials: JR
authors.lastname: Lynch
authors.forename: Haichen
authors.initials: H
authors.lastname: Wang
authors.forename: Brian
authors.initials: B
authors.lastname: Mace
authors.forename: Stephen
authors.initials: S
authors.lastname: Leinenweber
authors.forename: David S
authors.initials: DS
authors.lastname: Warner
authors.forename: Ellen R
authors.initials: ER
authors.lastname: Bennett
authors.forename: Michael P
authors.initials: MP
authors.lastname: Vitek
authors.forename: Suzanne
authors.initials: S
authors.lastname: McKenna
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Laskowitz
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism / Q000494:pharmacology; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites / Q000502:physiology; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology; D001929:Brain Edema / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control; D001930:Brain Injuries / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000235:genetics; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004660:Encephalitis / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control; D016489:Head Injuries, Closed / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D007275:Injections, Intravenous; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000737:chemistry / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009069:Movement Disorders / Q000188:drug therapy / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology*; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D013997:Time Factors
chemical_list: D000893:Anti-Inflammatory Agents; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D016207:Cytokines; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D018696:Neuroprotective Agents; D010446:Peptide Fragments