Temporal and Spatial Dynamics of Cerebral Immune Cell Accumulation in Stroke

  • Mathias Gelderblom
    From the Department of Neurology (M.G., F.L., D.B., C.-U.C., D.A.S., E.O., C.G., T.M.), University Medical Center Hamburg–Eppendorf, Hamburg, Germany; the Institute of Neuroimmunology and Clinical Multiple Sclerosis Research (K.S., E.T.), Hamburg, Germany; and the Department of Pharmaceutical Sciences (T.V.A.), Texas Tech University Health Sciences Center, School of Pharmacy, Amarillo, Tex.
  • Frank Leypoldt
    From the Department of Neurology (M.G., F.L., D.B., C.-U.C., D.A.S., E.O., C.G., T.M.), University Medical Center Hamburg–Eppendorf, Hamburg, Germany; the Institute of Neuroimmunology and Clinical Multiple Sclerosis Research (K.S., E.T.), Hamburg, Germany; and the Department of Pharmaceutical Sciences (T.V.A.), Texas Tech University Health Sciences Center, School of Pharmacy, Amarillo, Tex.
  • Karin Steinbach
    From the Department of Neurology (M.G., F.L., D.B., C.-U.C., D.A.S., E.O., C.G., T.M.), University Medical Center Hamburg–Eppendorf, Hamburg, Germany; the Institute of Neuroimmunology and Clinical Multiple Sclerosis Research (K.S., E.T.), Hamburg, Germany; and the Department of Pharmaceutical Sciences (T.V.A.), Texas Tech University Health Sciences Center, School of Pharmacy, Amarillo, Tex.
  • Doerthe Behrens
    From the Department of Neurology (M.G., F.L., D.B., C.-U.C., D.A.S., E.O., C.G., T.M.), University Medical Center Hamburg–Eppendorf, Hamburg, Germany; the Institute of Neuroimmunology and Clinical Multiple Sclerosis Research (K.S., E.T.), Hamburg, Germany; and the Department of Pharmaceutical Sciences (T.V.A.), Texas Tech University Health Sciences Center, School of Pharmacy, Amarillo, Tex.
  • Chi-Un Choe
    From the Department of Neurology (M.G., F.L., D.B., C.-U.C., D.A.S., E.O., C.G., T.M.), University Medical Center Hamburg–Eppendorf, Hamburg, Germany; the Institute of Neuroimmunology and Clinical Multiple Sclerosis Research (K.S., E.T.), Hamburg, Germany; and the Department of Pharmaceutical Sciences (T.V.A.), Texas Tech University Health Sciences Center, School of Pharmacy, Amarillo, Tex.
  • Dominic A. Siler
    From the Department of Neurology (M.G., F.L., D.B., C.-U.C., D.A.S., E.O., C.G., T.M.), University Medical Center Hamburg–Eppendorf, Hamburg, Germany; the Institute of Neuroimmunology and Clinical Multiple Sclerosis Research (K.S., E.T.), Hamburg, Germany; and the Department of Pharmaceutical Sciences (T.V.A.), Texas Tech University Health Sciences Center, School of Pharmacy, Amarillo, Tex.
  • Thiruma V. Arumugam
    From the Department of Neurology (M.G., F.L., D.B., C.-U.C., D.A.S., E.O., C.G., T.M.), University Medical Center Hamburg–Eppendorf, Hamburg, Germany; the Institute of Neuroimmunology and Clinical Multiple Sclerosis Research (K.S., E.T.), Hamburg, Germany; and the Department of Pharmaceutical Sciences (T.V.A.), Texas Tech University Health Sciences Center, School of Pharmacy, Amarillo, Tex.
  • Ellen Orthey
    From the Department of Neurology (M.G., F.L., D.B., C.-U.C., D.A.S., E.O., C.G., T.M.), University Medical Center Hamburg–Eppendorf, Hamburg, Germany; the Institute of Neuroimmunology and Clinical Multiple Sclerosis Research (K.S., E.T.), Hamburg, Germany; and the Department of Pharmaceutical Sciences (T.V.A.), Texas Tech University Health Sciences Center, School of Pharmacy, Amarillo, Tex.
  • Christian Gerloff
    From the Department of Neurology (M.G., F.L., D.B., C.-U.C., D.A.S., E.O., C.G., T.M.), University Medical Center Hamburg–Eppendorf, Hamburg, Germany; the Institute of Neuroimmunology and Clinical Multiple Sclerosis Research (K.S., E.T.), Hamburg, Germany; and the Department of Pharmaceutical Sciences (T.V.A.), Texas Tech University Health Sciences Center, School of Pharmacy, Amarillo, Tex.
  • Eva Tolosa
    From the Department of Neurology (M.G., F.L., D.B., C.-U.C., D.A.S., E.O., C.G., T.M.), University Medical Center Hamburg–Eppendorf, Hamburg, Germany; the Institute of Neuroimmunology and Clinical Multiple Sclerosis Research (K.S., E.T.), Hamburg, Germany; and the Department of Pharmaceutical Sciences (T.V.A.), Texas Tech University Health Sciences Center, School of Pharmacy, Amarillo, Tex.
  • Tim Magnus
    From the Department of Neurology (M.G., F.L., D.B., C.-U.C., D.A.S., E.O., C.G., T.M.), University Medical Center Hamburg–Eppendorf, Hamburg, Germany; the Institute of Neuroimmunology and Clinical Multiple Sclerosis Research (K.S., E.T.), Hamburg, Germany; and the Department of Pharmaceutical Sciences (T.V.A.), Texas Tech University Health Sciences Center, School of Pharmacy, Amarillo, Tex.

抄録

<jats:p> <jats:bold> <jats:italic>Background and Purpose—</jats:italic> </jats:bold> Ischemic stroke leads to significant morbidity and mortality in the Western world. Early reperfusion strategies remain the treatment of choice but can initiate and augment an inflammatory response causing secondary brain damage. The understanding of postischemic inflammation is very limited. The objectives of this study were to define the temporal and spatial infiltration of immune cell populations and their activation patterns in a murine cerebral ischemia–reperfusion injury model. </jats:p> <jats:p> <jats:bold> <jats:italic>Methods—</jats:italic> </jats:bold> Transient middle cerebral artery occlusion was induced for 1 hour followed by 12-hour to 7-day reperfusion in C57/BL6 mice. Immunohistochemistry and flow cytometry were used to quantify the infiltrating immune cell subsets. </jats:p> <jats:p> <jats:bold> <jats:italic>Results—</jats:italic> </jats:bold> Accumulation of microglia and infiltration of the ischemic hemisphere by macrophages, lymphocytes, and dendritic cells (DCs) preceded the neutrophilic influx. DCs were found to increase 20-fold and constituted a substantial proportion of infiltrating cells. DCs exhibited a significant upregulation of major histocompatibility complex II and major histocompatibility complex II high-expressing DCs were found 100 times more abundant than in sham conditions. Upregulation of the costimulatory molecule CD80 was observed in DCs and microglial cells but did not further increase in major histocompatibility complex II high-expressing DCs. No lymphocyte activation was observed. Additionally, regulatory immune cells (natural killer T-cells, CD4 <jats:sup>−</jats:sup> /CD8 <jats:sup>−</jats:sup> T lymphocytes) cumulated in the ischemic hemisphere. </jats:p> <jats:p> <jats:bold> <jats:italic>Conclusion—</jats:italic> </jats:bold> This study provides a detailed analysis of the temporal dynamics of immune cell accumulation in a rodent stroke model. The peculiar activation pattern and massive increase of antigen-presenting cells in temporal conjunction with regulatory cells might provide additional insight into poststroke immune regulation. </jats:p>

収録刊行物

  • Stroke

    Stroke 40 (5), 1849-1857, 2009-05

    Ovid Technologies (Wolters Kluwer Health)

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