Acta Neuropathologica

, Volume 130, Issue 2, pp 215–231 | Cite as

Microglia inflict delayed brain injury after subarachnoid hemorrhage

  • Ulf C. Schneider
  • Anja-Maria Davids
  • Susan Brandenburg
  • Annett Müller
  • Anna Elke
  • Salima Magrini
  • Etienne Atangana
  • Kati Turkowski
  • Tobias Finger
  • Angelika Gutenberg
  • Claire Gehlhaar
  • Wolfgang Brück
  • Frank L. Heppner
  • Peter Vajkoczy
Original Paper

Abstract

Inflammatory changes have been postulated to contribute to secondary brain injury after aneurysmal subarachnoid hemorrhage (SAH). In human specimens after SAH as well as in experimental SAH using mice, we show an intracerebral accumulation of inflammatory cells between days 4 and 28 after the bleeding. Using bone marrow chimeric mice allowing tracing of all peripherally derived immune cells, we confirm a truly CNS-intrinsic, microglial origin of these immune cells, exhibiting an inflammatory state, and rule out invasion of myeloid cells from the periphery into the brain. Furthermore, we detect secondary neuro-axonal injury throughout the time course of SAH. Since neuronal cell death and microglia accumulation follow a similar time course, we addressed whether the occurrence of activated microglia and neuro-axonal injury upon SAH are causally linked by depleting microglia in vivo. Given that the amount of neuronal cell death was significantly reduced after microglia depletion, we conclude that microglia accumulation inflicts secondary brain injury after SAH.

Keywords

Microglia Inflammation Subarachnoid hemorrhage Delayed brain injury 

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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Ulf C. Schneider
    • 1
    • 2
  • Anja-Maria Davids
    • 1
    • 2
  • Susan Brandenburg
    • 2
  • Annett Müller
    • 2
  • Anna Elke
    • 2
  • Salima Magrini
    • 2
  • Etienne Atangana
    • 2
    • 3
  • Kati Turkowski
    • 2
  • Tobias Finger
    • 1
    • 2
  • Angelika Gutenberg
    • 3
  • Claire Gehlhaar
    • 5
  • Wolfgang Brück
    • 4
  • Frank L. Heppner
    • 5
  • Peter Vajkoczy
    • 1
    • 2
  1. 1.Department of NeurosurgeryCharité, Universitätsmedizin BerlinBerlinGermany
  2. 2.Experimental NeurosurgeryCharité, Universitätsmedizin BerlinBerlinGermany
  3. 3.Department of NeurosurgeryUniversitätsmedizin GöttingenGöttingenGermany
  4. 4.Institute of NeuropathologyUniversitätsmedizin GöttingenGöttingenGermany
  5. 5.Department of NeuropathologyCharité, Universitätsmedizin BerlinBerlinGermany

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