A novel therapeutic derived from apolipoprotein E reduces brain inflammation and improves outcome after closed head injury. Exp Neurol 2005 Mar;192(1):109-16
Date
02/09/2005Pubmed ID
15698624DOI
10.1016/j.expneurol.2004.11.014Scopus ID
2-s2.0-13444266299 (requires institutional sign-in at Scopus site) 119 CitationsAbstract
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.
Author List
Lynch JR, Wang H, Mace B, Leinenweber S, Warner DS, Bennett ER, Vitek MP, McKenna S, Laskowitz DTMESH terms used to index this publication - Major topics in bold
AnimalsAnti-Inflammatory Agents
Apolipoprotein E4
Apolipoproteins E
Binding Sites
Blood-Brain Barrier
Brain Edema
Brain Injuries
Cytokines
Disease Models, Animal
Dose-Response Relationship, Drug
Encephalitis
Head Injuries, Closed
Injections, Intravenous
Low Density Lipoprotein Receptor-Related Protein-1
Male
Mice
Mice, Inbred C57BL
Movement Disorders
Neuroprotective Agents
Peptide Fragments
Recovery of Function
Time Factors
