Article
Inflammatory preconditioning against microglia-induced neuronal cell death following subarachnoid haemorrhage (SAH)
Inflammatorische Präkonditionierung gegen durch Mikroglia-Aktivierung verursachten neuronalen Schaden nach Subarachnoidalblutung
Search Medline for
Authors
-
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
| Published: | May 8, 2019 |
|---|
Outline
Text
Objective: Inflammation plays a pivotal role in secondary brain injury following SAH. Activated microglia (MG) have been shown to induce neuronal injury on top of early brain injury between 4 and fourteen days after the bleeding.
Preconditioning is the application of a minor stimulus of any kind to prepare the organism for a following more harmful stimulus of the same kind (e.g. hypoxic preconditioning for ischemic stroke). To test the effect of an inflammatory preconditioning, we used a murine model for experimental SAH (eSAH).
Methods: C57Bl/6 mice underwent eSAH using a filament perforation model. SAH was verified in a 7T-mouse MRI. One hour after the bleeding, mice were treated with lipopolysaccharide intraperitoneally (SAH LPS, 0.6mg/kg, n=6), or with saline (SAH PBS, n=6). Sham-operated mice served as controls (Sham, n=6). The number of MG within the brains was counted (Iba-1 immunofluorescence), as well as the number of apoptotic neurons (NeuN co TUNEL), to quantify the severity of secondary brain injury.
Results: SAH lead to a significantly increased number of MG, when compared to sham. Preconditioning with systemically applied LPS lead to a significantly lower number of MG compared to SAH PBS, yet, the count was still substantially higher than in the sham group (SAH PBS 32±2 vs SAH LPS 17±2 vs Sham 12±1; p<0.05 between all groups, cells/HPF). Reduction of MG lead to a decrease of dying neurons in a comparative fashion (SAH PBS 146±10 vs SAH LPS 77±9 vs Sham 12±2; p<0.05 SAH PBS vs both groups; cells/HPF).
Conclusion: Inflammatory preconditioning leads to a significant reduction of MG-induced neuronal cell death following eSAH in mice, even if the precondition is done systemically, after the ictus of the bleeding. It therefore might provide a clinically relevant treatment option for secondary brain injury following SAH.
