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  • Implantation of Neural Stem Cells Carrying Galectin-1 Elicits Long-term Neuroprotection Against Traumatic Brain Injury in Mice

    Final Number:
    1373

    Authors:
    Ling Chen MD, PhD; Anthony K.F. Liou; Feng Zhang; Chen Jun

    Study Design:
    Laboratory Investigation

    Subject Category:

    Meeting: Congress of Neurological Surgeons 2016 Annual Meeting

    Introduction: Galectin-1 (gal-1) is a ß-galactoside-binding lectin that is normally expressed in the brain at low levels and upregulated after injury. Gal-1 is known to protect against ischemic brain injury. The present study investigates the protective effects of gal-1 against traumatic brain injury (TBI). Control neural stem cells (NE-4C) or cells carrying the secretory form of gal-1 (s-NE-4C) were implanted into the corpus callosum and striatum of adult mouse brains 1 hour after controlled cortical impact, a well-established model of TBI. Neurological performance and lesion volumes were assessed up to 35 days post-TBI. The potential mechanisms underlying gal-1-mediated protection were also investigated. s-NE-4C implantation led to more potent neuroprotection than NE-4C alone, as shown by reductions in neurological dysfunction, lesion size, and hippocampal CA3 neuronal death. Gal-1 treatment protected cultured oligodendrocyte progenitor cells against excitotoxicity and reduced the production of tumor necrosis factor-a and nitric oxide after lipopolysaccharide stimulation in microglial cell cultures.

    Methods: All animal experiments were approved by the University of Pittsburgh Institutional Animal Care and Use Committee, and performed in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals.

    Results: Generation of s-NE-4C cells and their fate after implantation into the brain.Neural stem cell transplantation attenuates behavioral deficits.Neural stem cell implantation reduces lesion size and hippocampal CA3 neuronal death.Neural stem cells attenuate oligodendrocyte precursor cell death and white matter injury.Gal-1 suppresses secretion of NO and TNF-a in activated microglia.

    Conclusions: Our novel findings suggest that implantation of neural stem cells carrying the secreted form of gal-1 provides potent neuroprotection against TBI by targeting gray matter, white matter, and microglial function.

    Patient Care: implantation of neural stem cells carrying the secreted form of gal-1 provides potent neuroprotection against TBI by targeting gray matter, white matter, and microglial function.

    Learning Objectives: s-NE-4C implantation reduced white matter injury and microglial activation after TBI in vivo

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