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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Anti-Inflammatory Agents / metabolism
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Anti-Inflammatory Agents / pharmacology
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Apolipoprotein E4
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Apolipoproteins E / chemistry
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Apolipoproteins E / genetics
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Apolipoproteins E / metabolism*
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Binding Sites / physiology
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Blood-Brain Barrier / drug effects
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Blood-Brain Barrier / physiology
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Brain Edema / drug therapy
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Brain Edema / physiopathology
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Brain Edema / prevention & control
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Brain Injuries / complications
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Brain Injuries / drug therapy*
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Brain Injuries / physiopathology
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Cytokines / antagonists & inhibitors
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Cytokines / genetics
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Disease Models, Animal
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Dose-Response Relationship, Drug
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Encephalitis / drug therapy*
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Encephalitis / etiology
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Encephalitis / prevention & control
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Head Injuries, Closed / complications
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Head Injuries, Closed / drug therapy*
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Head Injuries, Closed / physiopathology
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Injections, Intravenous
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Low Density Lipoprotein Receptor-Related Protein-1 / chemistry
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Low Density Lipoprotein Receptor-Related Protein-1 / metabolism
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Male
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Mice
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Mice, Inbred C57BL
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Movement Disorders / drug therapy
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Movement Disorders / physiopathology
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Neuroprotective Agents / metabolism
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Neuroprotective Agents / pharmacology*
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Peptide Fragments / chemistry
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Peptide Fragments / metabolism
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Peptide Fragments / pharmacology*
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Recovery of Function / drug effects
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Recovery of Function / physiology
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Time Factors
Substances
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Anti-Inflammatory Agents
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Apolipoprotein E4
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Apolipoproteins E
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Cytokines
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Low Density Lipoprotein Receptor-Related Protein-1
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Neuroprotective Agents
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Peptide Fragments