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Role of microglia in a mouse model of paediatric traumatic brain injury.
Chhor, Vibol; Moretti, Raffaella; Le Charpentier, Tifenn; Sigaut, Stephanie; Lebon, Sophie; Schwendimann, Leslie; Oré, Marie-Virginie; Zuiani, Chiara; Milan, Valentina; Josserand, Julien; Vontell, Regina; Pansiot, Julien; Degos, Vincent; Ikonomidou, Chrysanthy; Titomanlio, Luigi; Hagberg, Henrik; Gressens, Pierre; Fleiss, Bobbi.
Afiliación
  • Chhor V; PROTECT, INSERM, Unversité Paris Diderot, Sorbonne Paris Cité, Paris, France; PremUP, Paris, France; Department of Anesthesia and Intensive Care, Georges Pompidou European Hospital, Paris, France.
  • Moretti R; PROTECT, INSERM, Unversité Paris Diderot, Sorbonne Paris Cité, Paris, France; PremUP, Paris, France; Università degli Studi di Udine, Udine, Italy.
  • Le Charpentier T; PROTECT, INSERM, Unversité Paris Diderot, Sorbonne Paris Cité, Paris, France; PremUP, Paris, France.
  • Sigaut S; PROTECT, INSERM, Unversité Paris Diderot, Sorbonne Paris Cité, Paris, France; PremUP, Paris, France.
  • Lebon S; PROTECT, INSERM, Unversité Paris Diderot, Sorbonne Paris Cité, Paris, France; PremUP, Paris, France.
  • Schwendimann L; PROTECT, INSERM, Unversité Paris Diderot, Sorbonne Paris Cité, Paris, France; PremUP, Paris, France.
  • Oré MV; PROTECT, INSERM, Unversité Paris Diderot, Sorbonne Paris Cité, Paris, France; PremUP, Paris, France.
  • Zuiani C; PROTECT, INSERM, Unversité Paris Diderot, Sorbonne Paris Cité, Paris, France; PremUP, Paris, France.
  • Milan V; PROTECT, INSERM, Unversité Paris Diderot, Sorbonne Paris Cité, Paris, France; PremUP, Paris, France.
  • Josserand J; PROTECT, INSERM, Unversité Paris Diderot, Sorbonne Paris Cité, Paris, France; PremUP, Paris, France.
  • Vontell R; Department of Perinatal Imaging and Health, Department of Division of Imaging Sciences and Biomedical Engineering, King's College London, King's Health Partners, St. Thomas' Hospital, London SE1 7EH, United Kingdom.
  • Pansiot J; PROTECT, INSERM, Unversité Paris Diderot, Sorbonne Paris Cité, Paris, France; PremUP, Paris, France.
  • Degos V; PROTECT, INSERM, Unversité Paris Diderot, Sorbonne Paris Cité, Paris, France; PremUP, Paris, France; Department of Anesthesia and Intensive Care, Pitié Salpétrière Hospital, F-75013 Paris, France.
  • Ikonomidou C; Department of Neurology, University of Wisconsin, Madison, WI, USA.
  • Titomanlio L; PROTECT, INSERM, Unversité Paris Diderot, Sorbonne Paris Cité, Paris, France; PremUP, Paris, France.
  • Hagberg H; Department of Perinatal Imaging and Health, Department of Division of Imaging Sciences and Biomedical Engineering, King's College London, King's Health Partners, St. Thomas' Hospital, London SE1 7EH, United Kingdom; Department of Clinical Sciences, Sahlgrenska Academy/East Hospital, Gothenburg Unive
  • Gressens P; PROTECT, INSERM, Unversité Paris Diderot, Sorbonne Paris Cité, Paris, France; PremUP, Paris, France; Department of Perinatal Imaging and Health, Department of Division of Imaging Sciences and Biomedical Engineering, King's College London, King's Health Partners, St. Thomas' Hospital, London SE1 7EH,
  • Fleiss B; PROTECT, INSERM, Unversité Paris Diderot, Sorbonne Paris Cité, Paris, France; PremUP, Paris, France; Department of Perinatal Imaging and Health, Department of Division of Imaging Sciences and Biomedical Engineering, King's College London, King's Health Partners, St. Thomas' Hospital, London SE1 7EH,
Brain Behav Immun ; 63: 197-209, 2017 Jul.
Article en En | MEDLINE | ID: mdl-27818218
The cognitive and behavioural deficits caused by traumatic brain injury (TBI) to the immature brain are more severe and persistent than TBI in the mature brain. Understanding this developmental sensitivity is critical as children under four years of age sustain TBI more frequently than any other age group. Microglia (MG), resident immune cells of the brain that mediate neuroinflammation, are activated following TBI in the immature brain. However, the type and temporal profile of this activation and the consequences of altering it are still largely unknown. In a mouse model of closed head weight drop paediatric brain trauma, we characterized i) the temporal course of total cortical neuroinflammation and the phenotype of ex vivo isolated CD11B-positive microglia/macrophage (MG/MΦ) using a battery of 32 markers, and ii) neuropathological outcome 1 and 5days post-injury. We also assessed the effects of targeting MG/MΦ activation directly, using minocycline a prototypical microglial activation antagonist, on these processes and outcome. TBI induced a moderate increase in both pro- and anti-inflammatory cytokines/chemokines in the ipsilateral hemisphere. Isolated cortical MG/MΦ expressed increased levels of markers of endogenous reparatory/regenerative and immunomodulatory phenotypes compared with shams. Blocking MG/MΦ activation with minocycline at the time of injury and 1 and 2days post-injury had only transient protective effects, reducing ventricular dilatation and cell death 1day post-injury but having no effect on injury severity at 5days. This study demonstrates that, unlike in adults, the role of MG/MΦ in injury mechanisms following TBI in the immature brain may not be negative. An improved understanding of MG/MΦ function in paediatric TBI could support translational efforts to design therapeutic interventions.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Microglía / Lesiones Traumáticas del Encéfalo / Activación de Macrófagos Límite: Animals Idioma: En Revista: Brain Behav Immun Asunto de la revista: ALERGIA E IMUNOLOGIA / CEREBRO / PSICOFISIOLOGIA Año: 2017 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Países Bajos
Texto completo
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PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Microglía / Lesiones Traumáticas del Encéfalo / Activación de Macrófagos Límite: Animals Idioma: En Revista: Brain Behav Immun Asunto de la revista: ALERGIA E IMUNOLOGIA / CEREBRO / PSICOFISIOLOGIA Año: 2017 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Países Bajos