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ApoE mimetic ameliorates motor deficit and tissue damage in rat spinal cord injury

Authors

  • Ruihua Wang,

    1. The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
    2. Department of Anesthesiology, Multidisciplinary Neuroprotection Laboratories, Duke University Medical Center, Durham, North Carolina
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    • R. Wang and J. Hong contributed equally to this work.

  • Jun Hong,

    1. Department of Anesthesiology, Multidisciplinary Neuroprotection Laboratories, Duke University Medical Center, Durham, North Carolina
    2. Tangshan Gongren Hospital, Hebei, China
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    • R. Wang and J. Hong contributed equally to this work.

  • Miaomiao Lu,

    1. Department of Anesthesiology, Multidisciplinary Neuroprotection Laboratories, Duke University Medical Center, Durham, North Carolina
    2. The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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  • Jessica E. Neil,

    1. Cognosci Inc., Research Triangle Park, North Carolina
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  • Michael P. Vitek,

    1. Cognosci Inc., Research Triangle Park, North Carolina
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  • Xiaozhi Liu,

    1. Department of Anesthesiology, Multidisciplinary Neuroprotection Laboratories, Duke University Medical Center, Durham, North Carolina
    2. The Fifth Central Hospital of Tianjin, Tianjin, China
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  • David S. Warner,

    1. Department of Anesthesiology, Multidisciplinary Neuroprotection Laboratories, Duke University Medical Center, Durham, North Carolina
    2. Department of Surgery (Neurosurgery), Duke University Medical Center, Durham, North Carolina
    3. Department of Neurobiology, Duke University Medical Center, Durham, North Carolina
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  • Fengqiao Li,

    1. Cognosci Inc., Research Triangle Park, North Carolina
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  • Huaxin Sheng

    Corresponding author
    1. Department of Anesthesiology, Multidisciplinary Neuroprotection Laboratories, Duke University Medical Center, Durham, North Carolina
    • Correspondence to: Huaxin Sheng, MD, Department of Anesthesiology, Box 3094, Duke University Medical Center, Durham, NC 27710. E-mail: sheng001@mc.duke.edu

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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. © 2014 Wiley Periodicals, Inc.

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