TRANSLATIONAL RESEARCH The apoE-mimetic Peptide, COG1410, Improves Functional Recovery in a Murine Model of Intracerebral Hemorrhage Daniel T. Laskowitz • Beilei Lei • Hana N. Dawson • Haichen Wang • Steven T. Bellows • Dale J. Christensen • Michael P. Vitek • Michael L. James Published online: 12 October 2011 Ó Springer Science+Business Media, LLC 2011 Abstract Background Apolipoprotein E has previously been dem- onstrated to modulate acute brain injury responses, and administration of COG1410, an apoE-mimetic peptide derived from the receptor-binding region of apoE, improves outcome in preclinical models of acute neuro- logical injury. In the current study, we sought to establish the optimal dose and timing of peptide administration associated with improved functional outcome in a murine model of intracerebral hemorrhage (ICH). Methods Ten to twelve-week-old C57/BL6 male mice were injured by collagenase-induced ICH and randomly selected to receive either vehicle or one of four doses of COG1410 (0.5, 1, 2, or 4 mg/kg) via tail vein injection at 30 min after injury and then daily for 5 days. The injured mice were euthanized at various time points to assess inflammatory mediators, cerebral edema, and hematoma volume. Over the first 5 days following injury, vestibulomotor function was tested via Rotorod (RR) latency. After an optimal dose was demonstrated, a final cohort of animals was injured with ICH and randomly assigned to receive the first dose of COG1410 or vehicle at increasingly longer treatment initiation times after injury. The mice were then assessed for functional deficit via RR testing over the first 5 days following injury. Results The mice receiving 2 mg/kg of COG1410 after injury demonstrated reduced functional deficit, decreased D. T. Laskowitz Departments of Medicine (Neurology), Neurobiology, and Anesthesiology, Multidisciplinary Neuroprotection Laboratories, Duke University, Durham, NC, USA e-mail: Daniel.laskowitz@duke.edu B. Lei Department of Anesthesiology, Multidisciplinary Neuroprotection Laboratories, Duke University, Durham, NC, USA e-mail: beilei.lei@duke.edu H. N. Dawson Á H. Wang Department of Medicine (Neurology), Multidisciplinary Neuroprotection Laboratories, Duke University, Durham, NC, USA e-mail: hana.dawson@duke.edu H. Wang e-mail: haichen.wang@duke.edu S. T. Bellows Department of Anesthesiology, Duke University, Durham, NC, USA e-mail: steven.bellows@gmail.com D. J. Christensen Department of Medicine (Hematology), Duke University, Durham, NC, USA e-mail: dchristensen@cognosci.com D. J. Christensen Á M. P. Vitek Cognosci, Inc., Research Triangle Park, NC, USA e-mail: mvitek@cognosci.com M. P. Vitek Departments of Medicine (Neurology) and Neurobiology, Duke University, Durham, NC, USA M. L. James (&) Departments of Anesthesiology and Medicine (Neurology), Multidisciplinary Neuroprotection Laboratories, Duke University, DUMC 3094, Durham, NC 27710, USA e-mail: Michael.james@duke.edu 123 Neurocrit Care (2012) 16:316–326 DOI 10.1007/s12028-011-9641-5