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Early Targeting of L-Selectin on Leukocytes Promotes Recovery after Spinal Cord Injury, Implicating Novel Mechanisms of Pathogenesis.
McCreedy, D A; Lee, S; Sontag, C J; Weinstein, P; Olivas, A D; Martinez, A F; Fandel, T M; Trivedi, A; Lowell, C A; Rosen, S D; Noble-Haeusslein, L J.
Afiliación
  • McCreedy DA; Department of Neurological Surgery, University of California, San Francisco, CA 94143.
  • Lee S; J. David Gladstone Institutes, University of California, San Francisco, CA 94158.
  • Sontag CJ; Department of Laboratory Medicine, University of California, San Francisco, CA 94143.
  • Weinstein P; Department of Neurological Surgery, University of California, San Francisco, CA 94143.
  • Olivas AD; Brain and Spinal Injury Center, University of California, San Francisco, CA 94110.
  • Martinez AF; Department of Neurological Surgery, University of California, San Francisco, CA 94143.
  • Fandel TM; Department of Neurological Surgery, University of California, San Francisco, CA 94143.
  • Trivedi A; Department of Neurological Surgery, University of California, San Francisco, CA 94143.
  • Lowell CA; Department of Neurological Surgery, University of California, San Francisco, CA 94143.
  • Rosen SD; Department of Neurological Surgery, University of California, San Francisco, CA 94143.
  • Noble-Haeusslein LJ; Department of Neurological Surgery, University of California, San Francisco, CA 94143.
eNeuro ; 5(4)2018.
Article en En | MEDLINE | ID: mdl-30225356
L-selectin, a lectin-like receptor on all leukocyte classes, functions in adhesive and signaling roles in the recruitment of myeloid cells from the blood to sites of inflammation. Here, we consider L-selectin as a determinant of neurological recovery in a murine model of spinal cord injury (SCI). Spinal cord-injured, L-selectin knock-out (KO) mice (male) showed improved long-term recovery with greater white matter sparing relative to wild-type (WT) mice and reduced oxidative stress in the injured cord at 72 h post-SCI. There was a partial and transient reduction in accumulation of neutrophils in the injured spinal cords of KOs at 24 h post-injury. To complement these findings with KO mice, we sought a pharmacologic means for lowering L-selectin levels. We found that diclofenac, a nonsteroidal anti-inflammatory drug (NSAID), induced the shedding of L-selectin from the cell surface of myeloid subsets, specifically neutrophils and non-classical monocytes, in the blood and the injured spinal cord. Diclofenac administration to injured WT mice enhanced neurological recovery to a level comparable to that of KOs but did not improve recovery in KOs. While diclofenac treatment had no effect on myeloid cell accumulation, there was a reduction in oxidative stress at 72 h post-SCI. These findings implicate L-selectin in secondary pathogenesis beyond a role in leukocyte recruitment and raise the possibility of repurposing diclofenac for the treatment of SCI.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Traumatismos de la Médula Espinal / Antiinflamatorios no Esteroideos / Diclofenaco / Estrés Oxidativo / Selectina L / Células Mieloides / Inflamación / Leucocitos Tipo de estudio: Etiology_studies / Prognostic_studies Límite: Animals Idioma: En Revista: ENeuro Año: 2018 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
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XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Traumatismos de la Médula Espinal / Antiinflamatorios no Esteroideos / Diclofenaco / Estrés Oxidativo / Selectina L / Células Mieloides / Inflamación / Leucocitos Tipo de estudio: Etiology_studies / Prognostic_studies Límite: Animals Idioma: En Revista: ENeuro Año: 2018 Tipo del documento: Article Pais de publicación: Estados Unidos