title: Neuroprotective and nootropic actions of a novel cyclized dipeptide after controlled cortical impact injury in mice.
abstract: 1-ARA-35b (35b) is a cyclized dipeptide that shows considerable neuroprotective activity in vitro and improves neurologic recovery after fluid percussion-induced traumatic brain injury in rats. The authors evaluated the effects of treatment with 35b in mice subjected to controlled cortical impact brain injury. Animals treated with intravenous 35b after traumatic injury showed significantly enhanced recovery of beam walking and place learning functions compared with vehicle-treated controls, in addition to reduced lesion volumes. Beneficial effects were dose related and showed an inverted U-shaped dose-response curve between 0.1 and 10 mg/kg. Protective actions were found when the drug was administered initially at 30 minutes or 1, 4, or 8 hours, but not at 24 hours, after trauma. In separate experiments, rats treated with 35b on days 7 through 10 after injury showed remarkably improved place learning in comparison with injured controls. These studies confirm and extend the neuroprotective effects of this diketopiperazine in traumatic brain injury. In addition, they show that 35b has a relatively wide therapeutic window and improves cognitive function after both acute and chronic injury.
authors.affiliation: Department of Neuroscience, Georgetown University Medical Center, 3970 Reservoir Road NW, Room EP-12, Washington, DC 20057, USA. fadena@georgetown.edu
authors.forename: Alan I
authors.initials: AI
authors.lastname: Faden
authors.forename: Gerard B
authors.initials: GB
authors.lastname: Fox
authors.forename: Xiao
authors.initials: X
authors.lastname: Di
authors.forename: Susan M
authors.initials: SM
authors.lastname: Knoblach
authors.forename: Ibolja
authors.initials: I
authors.lastname: Cernak
authors.forename: Paul
authors.initials: P
authors.lastname: Mullins
authors.forename: Maria
authors.initials: M
authors.lastname: Nikolaeva
authors.forename: Alan P
authors.initials: AP
authors.lastname: Kozikowski
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000473:pathology / Q000503:physiopathology* / Q000523:psychology*; D002540:Cerebral Cortex / Q000293:injuries / Q000473:pathology* / Q000503:physiopathology; D004151:Dipeptides / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018697:Nootropic Agents / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D014949:Wounds, Nonpenetrating / Q000473:pathology / Q000503:physiopathology* / Q000523:psychology*
chemical_list: C472684:1-ARA-35b; D004151:Dipeptides; D018696:Neuroprotective Agents; D018697:Nootropic Agents; D010456:Peptides, Cyclic; D010879:Piperazines