COG1410, a novel apolipoprotein E-based peptide, improves functional recovery in a murine model of traumatic brain injury.

COG1410, a novel apolipoprotein E-based peptide, improves functional recovery in a murine model of traumatic brain injury. Research Abstract Details 

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COG1410, a novel apolipoprotein E-based peptide, improves functional recovery in a murine model of traumatic brain injury. Abstract Text:

Daniel T Laskowitz,Suzanne E McKenna,Pingping Song,Haichen Wang,Lori Durham,Nolan Yeung,Dale Christensen,Michael P Vitek,

Traumatic brain injury (TBI) is a silent epidemic affecting approximately 1.4 million Americans annually, at an estimated annual cost of $60 billion in the United States alone. Despite an increased understanding of the pathophysiology of closed head injury, there remains no pharmacological intervention proven to improve functional outcomes in this setting. Currently, the existing standard of care for TBI consists primarily of supportive measures. Apolipoprotein E (apoE) is the primary apolipoprotein synthesized in the brain in response to injury, where it modulates several components of the neuroinflammatory cascade associated with TBI. We have previously demonstrated that COG133, an apoE mimetic peptide, improved functional outcomes and attenuated neuronal death when administered as a single intravenous injection at 30 min post-TBI in mice. Using the principles of rational drug design, we developed a more potent analog, COG1410, which expands the therapeutic window for the treatment of TBI by a factor of four, from 30 min to 2 h. Mice that received a single intravenous injection of COG1410 at 120 min post-TBI exhibited significant improvement on a short term test of vestibulomotor function and on a long term test of spatial learning and memory. This was associated with a significant attenuation of microglial activation and neuronal death in the hippocampus, the neuroanatomical substrate for learning and memory. Rationally derived apoE mimetic peptides have been demonstrated to exert neuroprotective and anti-inflammatory effects in vitro and in clinically relevant models of brain injury. This represents a novel therapeutic strategy in the treatment of TBI.

COG1410, a novel apolipoprotein E-based peptide, improves functional recovery in a murine model of traumatic brain injury. Publishing Authors By Initials

DT Laskowitz,SE McKenna,P Song,H Wang,L Durham,N Yeung,D Christensen,MP Vitek,

For similar diagnosis: prognosis: treatment outcome research abstracts see: diagnosis: prognosis: treatment outcome research

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COG1410, a novel apolipoprotein E-based peptide, improves functional recovery in a murine model of traumatic brain injury. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Journal of neurotrauma

VOLUME: 24

Page Numbers: 1093-107

Journal Abbreviation: J. Neurotrauma

ISSN: 0897-7151

DAY: 29

MONTH: Jul

YEAR: 2007

COG1410, a novel apolipoprotein E-based peptide, improves functional recovery in a murine model of traumatic brain injury. Information

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LANGUAGE: eng

NlmUniqueID: 8811626

COG1410, a novel apolipoprotein E-based peptide, improves functional recovery in a murine model of traumatic brain injury. Keywords Mesh Terms:

KEYWORDS: Treatment Outcome

MESH TERMS: physiology

Chemical & Substance for Abstract: COG1410, a novel apolipoprotein E-based peptide, improves functional recovery in a murine model of traumatic brain injury. Information

Substance Name: Peptides

Registry Number: 0

Grant and Affiliation Information for COG1410, a novel apolipoprotein E-based peptide, improves functional recovery in a murine model of traumatic brain injury.

AFFILIATION: Division of Neurology, Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA.

Country: United States

AGENCY: United States NINDS

GRANT: R21NS4487

ACRONYM: NS

MEDLINETA: J Neurotrauma

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