Neuroprotective pentapeptide CN-105 improves functional and histological outcomes in a murine model of intracerebral hemorrhage.
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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.
Published Version (Please cite this version)10.1038/srep34834
Publication InfoAcheson, Shawn K; Dubois, Laura; James, Michael Lucas; Lascola, Christopher David; Laskowitz, Daniel Todd; Lei, Beilei; ... Zhou, Guanen (2016). Neuroprotective pentapeptide CN-105 improves functional and histological outcomes in a murine model of intracerebral hemorrhage. Sci Rep, 6. pp. 34834. 10.1038/srep34834. Retrieved from http://hdl.handle.net/10161/14242.
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Assistant Professor in Psychiatry and Behavioral Sciences
In collaboration with Dr. Scott Swartzwelder, research in our lab has focused on the neurodevelopmental effects of alcohol and other drugs of abuse. In particular, we have been interested in how and why adolescents are more sensitive to some effects of ethanol and THC (e.g., learning and memory) and less sensitive to other effects (e.g., sedation). Beginning in Fall 2011, my lab will begin a new line of research focused on potential pharmacotherapies for TBI and the basic underlying mechani
Associate Professor of Anesthesiology
I have an extensive background in neuroanesthesia and neurointensive care and a special research interest in translational and clinical research aspects of intracerebral hemorrhage. After completing residencies in neurology and anesthesiology with fellowships in neurocritical care, neuroanesthesia, and vascular neurology, I developed a murine model of intracerebral hemorrhage in the Multidisciplinary Neuroprotection Laboratories at Duke University. After optimization of the model, I h
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Professor of Neurology
Our laboratory uses molecular biology, cell culture, and animal modeling techniques to examine the CNS response to acute injury. In particular, our laboratory examines the role of microglial activation and the endogenous CNS inflammatory response in exacerbating secondary injury following acute brain insult. Much of the in vitro work in this laboratory is dedicated to elucidating cellular responses to injury with the ultimate goal of exploring new therapeutic interventions in the clinical settin
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