Journal article
Neuronal Ablation of IKK2 Decreases Lesion Size and Improves Functional Outcome after Spinal Cord Injury in Mice
JSM neurosurgery and spine, v 5(3)
01 Jan 2017
PMID: 30035210
Abstract
Nuclear factor-kappa B (NF-κB) is a key modulator of inflammation and secondary injury responses in neurodegenerative disease, including spinal cord injury (SCI). Inhibition of astroglial NF-κB reduces inflammation, enhances oligodendrogenesis and improves functional recovery after SCI, however the contribution of neuronal NF-κB to secondary inflammatory responses following SCI has yet to be investigated. We demonstrate that conditional ablation of IKK2 in Synapsin 1-expressing neurons in mice (Syn1creIKK2
fl/fl
) reduces activation of the classical NF-κB signaling pathway, resulting in impaired motor function and altered memory retention under naïve conditions. Following induction of a moderate SCI phosphorylated NF-κB levels decreased in the spinal cord of Syn1creIKK2
fl/fl
mice compared to controls, resulting in improvement in functional recovery. Histologically, Syn1creIKK2
fl/fl
mice exhibited reduced lesion volume but comparable microglial/leukocyte responses after SCI. In parallel, interleukin (IL)-1β expression was significantly decreased within the lesioned spinal cord, whereas IL-5, IL-6, IL-10, tumor necrosis factor (TNF) and chemokine (C-X-C motif) ligand 1 were unchanged compared to control mice. We conclude that conditional ablation of IKK2 in neurons, resulting in reduced neuronal NF-B signaling, and lead to protective effects after SCI and propose the neuronal classical NF-κB pathway as a potential target for the development of new therapeutic, neuroprotective strategies for SCI.
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- Title
- Neuronal Ablation of IKK2 Decreases Lesion Size and Improves Functional Outcome after Spinal Cord Injury in Mice
- Creators
- Ditte Gry Ellman - Neurobiology Research, University of Southern Denmark, Denmark Department of Pathology, Odense University Hospital, Denmark The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, USA Department of Biology, Drexel University, USA Department of Biomedicine, Aarhus University, Denmark Department of Neurology, Odense University Hospital, Denmark Department of Clinical Research, University of Southern Denmark, DenmarkHans Gram Novrup - Neurobiology Research, University of Southern Denmark, Denmark Department of Pathology, Odense University Hospital, Denmark The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, USA Department of Biology, Drexel University, USA Department of Biomedicine, Aarhus University, Denmark Department of Neurology, Odense University Hospital, Denmark Department of Clinical Research, University of Southern Denmark, DenmarkLouise Helskov Jørgensen - Neurobiology Research, University of Southern Denmark, Denmark Department of Pathology, Odense University Hospital, Denmark The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, USA Department of Biology, Drexel University, USA Department of Biomedicine, Aarhus University, Denmark Department of Neurology, Odense University Hospital, Denmark Department of Clinical Research, University of Southern Denmark, DenmarkMinna Christiansen Lund - Neurobiology Research, University of Southern Denmark, Denmark Department of Pathology, Odense University Hospital, Denmark The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, USA Department of Biology, Drexel University, USA Department of Biomedicine, Aarhus University, Denmark Department of Neurology, Odense University Hospital, Denmark Department of Clinical Research, University of Southern Denmark, DenmarkMinna Yli-Karjanmaa - Neurobiology Research, University of Southern Denmark, Denmark Department of Pathology, Odense University Hospital, Denmark The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, USA Department of Biology, Drexel University, USA Department of Biomedicine, Aarhus University, Denmark Department of Neurology, Odense University Hospital, Denmark Department of Clinical Research, University of Southern Denmark, DenmarkPernille Marie Madsen - Neurobiology Research, University of Southern Denmark, Denmark Department of Pathology, Odense University Hospital, Denmark The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, USA Department of Biology, Drexel University, USA Department of Biomedicine, Aarhus University, Denmark Department of Neurology, Odense University Hospital, Denmark Department of Clinical Research, University of Southern Denmark, DenmarkJonas Heinrich Vienhues - Neurobiology Research, University of Southern Denmark, Denmark Department of Pathology, Odense University Hospital, Denmark The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, USA Department of Biology, Drexel University, USA Department of Biomedicine, Aarhus University, Denmark Department of Neurology, Odense University Hospital, Denmark Department of Clinical Research, University of Southern Denmark, DenmarkSafinaz Dursun - Neurobiology Research, University of Southern Denmark, Denmark Department of Pathology, Odense University Hospital, Denmark The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, USA Department of Biology, Drexel University, USA Department of Biomedicine, Aarhus University, Denmark Department of Neurology, Odense University Hospital, Denmark Department of Clinical Research, University of Southern Denmark, DenmarkJohn R. Bethea - Drexel UniversityKarin Lykke-Hartmann - Neurobiology Research, University of Southern Denmark, Denmark Department of Pathology, Odense University Hospital, Denmark The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, USA Department of Biology, Drexel University, USA Department of Biomedicine, Aarhus University, Denmark Department of Neurology, Odense University Hospital, Denmark Department of Clinical Research, University of Southern Denmark, DenmarkRoberta Brambilla - Drexel UniversityKate Lykke Lambertsen - Neurobiology Research, University of Southern Denmark, Denmark Department of Pathology, Odense University Hospital, Denmark The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, USA Department of Biology, Drexel University, USA Department of Biomedicine, Aarhus University, Denmark Department of Neurology, Odense University Hospital, Denmark Department of Clinical Research, University of Southern Denmark, Denmark
- Publication Details
- JSM neurosurgery and spine, v 5(3)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biology; College of Arts and Sciences; Drexel University
- Other Identifier
- 991020099716304721