title: ApoE mimetic ameliorates motor deficit and tissue damage in rat spinal cord injury.
abstract: Apolipoprotein E (apoE), a plasma protein responsible for transporting lipid and cholesterol, modulates responses of the central nervous system to injury. Small peptides derived from the receptor-binding region of apoE can simulate some important bioactivities of apoE holoprotein and offer neuroprotection against brain injury. We tested whether COG1410, an apoE-mimetic peptide, provides protection in a rat model of spinal cord injury (SCI). Traumatic injury was created at T8 by a cortical impact device. Injured rats were randomized to four treatment groups: vehicle, 0.15, 0.3, or 0.6 mg/kg COG1410; sham surgery rats received vehicle. Basso, Beattie, Bresnahan neurological score was evaluated prior to injury and at 1, 3, 7, and 14 days after injury. Histological changes were evaluated at 14 days. All injured rats lost body weight during the first week following injury. Body weight recovery was significantly improved in rats treated with COG1410. Mechanical impact resulted in severe motor deficit, and most animals had a BBB score of 0-1 at 24 hours postinjury. COG1410-treated rats showed significantly improved functional recovery and ameliorated motor deficit at 14 days postinjury. Histological analysis showed that COG1410 groups had a significantly reduced lesion size at the site of injury, a larger preserved luxol fast blue-stained area, and more visible neurons in the surrounding area of injury. Microglial activation was also significantly suppressed. These findings indicate that this apoE mimetic effectively improved neurological and histological outcome following SCI in rats, and the effect was associated with inhibition of microglial activation.
authors.affiliation: The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Department of Anesthesiology, Multidisciplinary Neuroprotection Laboratories, Duke University Medical Center, Durham, North Carolina.
authors.forename: Ruihua
authors.initials: R
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Hong
authors.forename: Miaomiao
authors.initials: M
authors.lastname: Lu
authors.forename: Jessica E
authors.initials: JE
authors.lastname: Neil
authors.forename: Michael P
authors.initials: MP
authors.lastname: Vitek
authors.forename: Xiaozhi
authors.initials: X
authors.lastname: Liu
authors.forename: David S
authors.initials: DS
authors.lastname: Warner
authors.forename: Fengqiao
authors.initials: F
authors.lastname: Li
authors.forename: Huaxin
authors.initials: H
authors.lastname: Sheng
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D056784:Leukoencephalopathies / Q000188:drug therapy / Q000209:etiology; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000473:pathology; D009069:Movement Disorders / Q000188:drug therapy* / Q000209:etiology*; D009460:Neurologic Examination; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000187:drug effects; D013119:Spinal Cord Injuries / Q000150:complications / Q000188:drug therapy / Q000473:pathology
chemical_list: D001057:Apolipoproteins E; C524548:COG1410
keywords: apoE; mimetic; outcome; rat; spinal cord injury