Artikel
Perivascular macrophages mediate microvasospasms after subarachnoid hemorrhage
Rolle perivaskulärer Makrophagen bei der posthämorrhagischen Mikrozirkulationsstörung nach experimenteller Subarachnoidalblutung
Suche in Medline nach
Autoren
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Julian Schwarting
- LMU Klinikum, Institut für Schlaganfall- und Demenzforschung (ISD), München, Deutschland
| Veröffentlicht: | 25. Mai 2022 |
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Gliederung
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Objective: Subarachnoid hemorrhage (SAH) is associated with acute and delayed cerebral ischemia resulting in high mortality and morbidity. The early phase after SAH (first 72 hours after hemorrhage) is characterized by perfusion deficits in the cerebral microcirculation. During this phase, spasms of arterial microvessels occur in patients and after experimental SAH. Recently, inactivation of perivascular macrophages (PVM) has been demonstrated to improve neurological outcome after experimental SAH; the mechanisms of this phenomenon, however, are not clear yet. Here, we investigated the role of perivascular macrophages (PVM) for the formation of microvasospasms in a filament perforation mouse model of subarachnoid hemorrhage
Methods: PVM were deleted in C57 Bl6 mice (male, 6-8 weeks old, 20-24 g bodyweight) seven days prior to SAH by injection of Clodronate (n=8) or sham liposomes (n=8) into the cisterna magna. Texas Red was injected intraperitoneally before SAH induction to label extravasated blood. SAH was then induced according to the MCA filament perforation model under continuous monitoring of CBF and ICP. Six hours after SAH induction, in-vivo 2-photon microscopy was performed via a cranial window after intraarterial injection of Fluorescein isothiocyanate. Caliber variations of the cerebral microvasculature were then analyzed in nine standardized regions of interest. Histological quantification of PVMs with CD206 and Laminin staining was performed after transcardial perfusion.
Results: PVM were predominantly located around 1st and 2nd order penetrating arterioles and were effectively depleted after Clodronate injection (p<0.01). After SAH, MVS mainly occurred in pial arteries (45 IQR 29 / animal), and 1st and 2ndorder penetrating arterioles (19 IQR 9 and 5 IQR 6 /animal). Macrophage depletion significantly reduced the number of MVS per animal (to 20 IQR 29 in pial vessels, p=.021, 5 IQR 5 in 1st , p=.006, and 2 IQR 3 in 2nd order penetrating arterioles, p=.039).
Conclusion: Our results suggest that PVM play a role in the formation of microvasospasms in the acute phase of SAH.
