Neuroprotective pentapeptide CN-105 improves functional and histological outcomes in a murine model of intracerebral hemorrhage.

Lei, Beilei

James, Michael L

Liu, Ji

Zhou, Guanen

Venkatraman, Talaignair N

Lascola, Christopher D

Acheson, Shawn K

Dubois, Laura G

Laskowitz, Daniel T

Wang, Haichen

England

2017-05-01T17:22:45Z

2017-05-01T17:22:45Z

2016-10-07

Presently, no pharmacological treatments have been demonstrated to improve long-term functional outcomes following intracerebral hemorrhage (ICH). Clinical evidence associates apolipoprotein E (apoE) genotype with ICH incidence and outcome. While apoE modifies neuroinflammatory responses through its adaptive role in glial downregulation, intact apoE holoprotein is too large to cross the blood-brain barrier (BBB). Therefore, we developed a 5-amino acid peptide - CN-105 - that mimics the polar face of the apoE helical domain involved in receptor interactions. In the current study, we investigated the therapeutic potential of CN-105 in a mouse model of ICH. Three doses of CN-105 (0.05 mg/kg) was administered by tail vein injection within 24 hours after ICH induction. Functional assessment showed durable improvement in vestibulomotor performance after CN-105 treatment, as quantified by increased Rotarod latencies on Days 1-5 post-ICH, and long-term improvement in neurocognitive performance, as quantified by reduced Morris water maze latencies on Days 29-32 post-ICH. Further, brain water content was significantly reduced, neuroinflammation was decreased and hippocampal CA3 neuronal survival was increased, although hemorrhage volume was not affected by CN-105. We concluded, therefore, that pentapeptide CN-105 improved short- and long-term neurobehavioral outcomes in a murine model of ICH, suggesting therapeutic potential for patients with acute ICH.

https://www.ncbi.nlm.nih.gov/pubmed/27713572

srep34834

2045-2322

https://hdl.handle.net/10161/14242

eng

Springer Science and Business Media LLC

Sci Rep

10.1038/srep34834

Neuroprotective pentapeptide CN-105 improves functional and histological outcomes in a murine model of intracerebral hemorrhage.

Journal article

James, Michael L|0000-0002-8715-5210

Lascola, Christopher D|0000-0002-8031-782X

Laskowitz, Daniel T|0000-0003-3430-8815

https://www.ncbi.nlm.nih.gov/pubmed/27713572

34834

Anesthesiology

Anesthesiology, Neuroanesthesia

Basic Science Departments

Clinical Science Departments

Duke

Duke Institute for Brain Sciences

Duke-UNC Center for Brain Imaging and Analysis

Institutes and Centers

Institutes and Provost's Academic Units

Neurobiology

Neurology

Neurology, Neurocritical Care

Psychiatry & Behavioral Sciences

Psychiatry & Behavioral Sciences, Translational Neuroscience

Radiology

Radiology, Neuroradiology

School of Medicine

University Institutes and Centers

Published online

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