title: Neuroprotective pentapeptide CN-105 improves functional and histological outcomes in a murine model of intracerebral hemorrhage.
abstract: 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.
authors.affiliation: Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Beilei
authors.initials: B
authors.lastname: Lei
authors.affiliation: Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710, USA.|Department of Neurology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Michael L
authors.initials: ML
authors.lastname: James
authors.affiliation: Department of Neurology, Huanhu Hospital, Tianjin, 300060, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Neurology, Huanhu Hospital, Tianjin, 300060, China.
authors.forename: Guanen
authors.initials: G
authors.lastname: Zhou
authors.affiliation: Department of Radiology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Talaignair N
authors.initials: TN
authors.lastname: Venkatraman
authors.affiliation: Department of Radiology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Lascola
authors.affiliation: Department of Psychiatry, Duke University Medical Center, Durham, NC 27710, USA.|Neurobiology Research Lab, Durham VA Medical Center, Durham, NC 27705, USA.
authors.forename: Shawn K
authors.initials: SK
authors.lastname: Acheson
authors.affiliation: Proteomics and Metabolomics Shared Resource, Duke University, Durham, NC 27710, USA.
authors.forename: Laura G
authors.initials: LG
authors.lastname: Dubois
authors.affiliation: Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710, USA.|Department of Neurology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Laskowitz
authors.affiliation: Department of Neurology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Haichen
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000737:chemistry; D001929:Brain Edema / Q000188:drug therapy; D056654:CA3 Region, Hippocampal / Q000187:drug effects / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D002543:Cerebral Hemorrhage / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D008297:Male; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D009842:Oligopeptides / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D045442:Rotarod Performance Test
chemical_list: D001057:Apolipoproteins E; D018696:Neuroprotective Agents; D009842:Oligopeptides