gms | German Medical Science

73. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
Joint Meeting mit der Griechischen Gesellschaft für Neurochirurgie

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

29.05. - 01.06.2022, Köln

Perivascular Macrophages, new players in post-SAH microcirculatory dysfunction?

Rolle perivaskulärer Makrophagen bei der posthämorrhagischen Mikrozirkulationsstörung nach experimenteller Subarachnoidalblutung

Meeting Abstract

  • presenting/speaker Julian Schwarting - Klinikum der Ludwig-Maximilians-Universität München, Institut für Schlaganfall- und Demenzforschung, München, Deutschland; Klinikum der Ludwig-Maximilians-Universität München, Neurochirurgische Klinik und Poliklinik, München, Deutschland
  • Xiangjiang Liu - Klinikum der Ludwig-Maximilians-Universität München, Institut für Schlaganfall- und Demenzforschung, München, Deutschland
  • presenting/speaker Nikolaus Plesnila - Klinikum der Ludwig-Maximilians-Universität München, Institut für Schlaganfall- und Demenzforschung, München, Deutschland
  • Nicole Angela Terpolilli - Klinikum der Ludwig-Maximilians-Universität München, Institut für Schlaganfall- und Demenzforschung, München, Deutschland; Klinikum der Ludwig-Maximilians-Universität München, Neurochirurgische Klinik und Poliklinik, München, Deutschland

Deutsche Gesellschaft für Neurochirurgie. 73. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Griechischen Gesellschaft für Neurochirurgie. Köln, 29.05.-01.06.2022. Düsseldorf: German Medical Science GMS Publishing House; 2022. DocV239

doi: 10.3205/22dgnc231, urn:nbn:de:0183-22dgnc2318

Published: May 25, 2022

© 2022 Schwarting et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.


Outline

Text

Objective: Acute and delayed cerebral ischemia is a main determinant of functional outcome after subarachnoid hemorrhage (SAH). Especially the first 72 hours after SAH are characterized by perfusion deficits in the cerebral microcirculation. 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. Given previous results and PVMs localization, we hypothesized that PVW are involved in the formation of microvascular spasms (MVS), thereby contributing to microcirculatory dysfunction. Here, we investigated the role of perivascular macrophages (PVM) after SAH in a filament perforation mouse model of subarachnoid hemorrhage.

Methods: PVM were depleted in C57 Bl6 mice (male, 6-8 weeks old, 20-24 g bodyweight) seven days prior to SAH by intracisternal injection of Clodronate (n=8); the control group received sham liposomes (n=8). Texas Red was injected intraperitoneally. Before SAH, Texas Reed was ip injected to label extravasated blood. SAH was then induced using the MCA filament perforation model under continuous monitoring of CBF and ICP. Six hours after SAH induction, in-vivo 2-photon microscopy was performed to directly visualize and assess the cerebral microcirculation via a cranial window after labelling plasma with Fluorescein isothiocyanate. Caliber variations of the cerebral microvasculature were then analyzed in nine standardized regions of interest. PVM location and depletion was verified using immunohistochemistry (CD206 and Laminin staining).

Results: PVM were predominantly located around 1st and 2nd order penetrating arterioles; Clodronate injection effectively depleted PVM compared to vehicle treated animals (p<0.01). After SAH, MVS mainly occurred in pial arteries (45 IQR 29 / animal), and 1st and 2nd order 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=0.021, 5 IQR 5 in 1st, p=0.006, and 2 IQR 3 in 2nd order penetrating arterioles, p=0.039).

Conclusion: PVM seem to be implicated in the formation of microvasospasms early after SAH, and, thus, contribute to posthemorrhagic microcirculatory dysfunction. Investigations to further clarify the timecourse, the underlying mechanisms, and possible therapeutic potential of PVM, are ongoing.