gms | German Medical Science

70. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
Joint Meeting mit der Skandinavischen Gesellschaft für Neurochirurgie

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

12.05. - 15.05.2019, Würzburg

Counteracting microglia (MG) development and activation leads to a decrease in inflammatory secondary brain injury after experimental subarachnoid haemorrhage (eSAH)

Die medikamentöse Hemmung der Mikroglia-Aktivierung führt zu einer Minderung der sekundären Hirnschädigung nach Subarachnoidalblutung

Meeting Abstract

Suche in Medline nach

  • presenting/speaker Ulf Schneider - Charité – Universitätsmedizin Berlin, Klinik für Neurochirurgie, Berlin, Deutschland
  • Rebecca Heinz - Charité – Universitätsmedizin Berlin, Klinik für Neurochirurgie, Berlin, Deutschland
  • Peter Vajkoczy - Charité – Universitätsmedizin Berlin, Klinik für Neurochirurgie, Berlin, Deutschland

Deutsche Gesellschaft für Neurochirurgie. 70. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Skandinavischen Gesellschaft für Neurochirurgie. Würzburg, 12.-15.05.2019. Düsseldorf: German Medical Science GMS Publishing House; 2019. DocP019

doi: 10.3205/19dgnc357, urn:nbn:de:0183-19dgnc3579

Veröffentlicht: 8. Mai 2019

© 2019 Schneider et al.
Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). Lizenz-Angaben siehe http://creativecommons.org/licenses/by/4.0/.


Gliederung

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Objective: Colony-stimulating factor-1-receptor (CSF1R) is known to be a key regulator for production and activation of macrophages and microglia. It has been correlated with mammary gland carcinogenesis, pancreatic cancer and myloic leukemia. An increased receptor causes MG to be more active. In Alzhemier’s diesease, elevated levels of CSF1R also lead to a disease progression. MG-driven inflammation inflicts secondary brain injury following SAH as well. To test whether counteraction of CSF1R ameliorates inflammation-triggered neuronal cell death following SAH, we evaluated a recombinant CSF1R-antagonist (PLX3397).

Methods: C57Bl6 mice underwent eSAH using filament perforation and were subsequently treated with PLX3397 (30mg/kg s.c. daily, n=6, SAH PLX group) or saline (n=6, SAH PBS group). Sham-operated animals served as controls (n=6, Sham group). Histologically stained brain sections were analyzed for the amount of MG (Iba-1) and TUNEL-positive neurons (NeuN) to evaluate inflammation effect and neuronal cell death, respectively.

Results: SAH lead to a significantly increased MG activation and a significant amount of neuronal cell death (SAH PBS vs Sham: 33±2 vs 12±2, MG; 146±10 vs 12±2, neuronal cell death, per HPF, p<0.05). Daily treatment with PLX3397 led to a complete reduction of MG activation to sham level (10±1). The amount of neuronal injury was lower than in SAH PBS animals, yet still higher than in sham animals (17±2, p<0.05 vs both groups).

Conclusion: Targeting MG development and activation, leads to the expected abolishment of MG-triggered inflammation within mice brains after eSAH, and reduced neuronal cell death, respectively. Yet, the effect on neuronal cell death was less pronounced than on MG activation. Still CSF1R might become an interesting target for the clinical treatment of secondary brain injury following SAH.