Role of perivascular and meningeal macrophages in outcome following experimental subarachnoid hemorrhage

Abstract

The distribution and clearance of erythrocytes after subarachnoid hemorrhage (SAH) is poorly understood. We aimed to characterize the distribution of erythrocytes after SAH and the cells involved in their clearance. To visualize erythrocyte distribution, we injected fluorescently-labelled erythrocytes into the prechiasmatic cistern of mice. 10 minutes after injection, we found labelled erythrocytes in the subarachnoid space and ventricular system, and also in the perivascular spaces surrounding large penetrating arterioles. 2 and 5 days after SAH, fluorescence was confined within leptomeningeal and perivascular cells. We identified the perivascular cells as perivascular macrophages based on their morphology, location, Iba-1 immunoreactivity and preferential uptake of FITC-dextran. We subsequently depleted meningeal and perivascular macrophages 2 days before or 3 hours after SAH with clodronate liposomes. At day 5 after SAH, we found increased blood deposition in mice treated prior to SAH, but not those treated after. Treatment post-SAH improved neurological scoring, reduced neuronal cell death and perivascular inflammation, whereas pre-treatment only reduced perivascular inflammation. Our data indicate that after SAH, erythrocytes are distributed throughout the subarachnoid space extending into the perivascular spaces of parenchymal arterioles. Furthermore, meningeal and perivascular macrophages are involved in erythrocyte uptake and play an important role in outcome after SAH.

Living on the Edge of the CNS: Meninges Cell Diversity in Health and Disease

“…In a study investigating the contribution of meninges-located mast cells in stroke pathology, depletion of mast cells resulted in decreased levels of neuroinflammation, brain swelling, and infarct size following stroke and this was partially mediated by mast-cell derived IL-6 ( Arac et al, 2019 ; Figure 3C ). Similarly, in a sub-arachnoid hemorrhage model, depletion of macrophages in the leptomeninges and perivascular spaces surrounding large arterioles prior to injury results in improved neurological scoring and reduced levels of inflammation and neuronal cell death ( Wan et al, 2021 ).…”

CD47 Blockade Accelerates Blood Clearance and Alleviates Early Brain Injury After Experimental Subarachnoid Hemorrhage

“…Besides, we focus on the CD47-SIRP axis of microglia in regulating erythrophagocytosis, though other CNS macrophages likely play a role in neuroinflammation. Previous studies have suggested that resident microglia rather than infiltrating macrophages are involved in neuroinflammation and blood clearance after SAH, but recent studies have shown that the immune cells of choroid plexus and meningeal/perivascular macrophages also play an important role in outcome after SAH (40,41). The exact mechanism of CNS border-associated macrophages (BAMs) remains to be elucidated.…”

Inflammation and Anti-Inflammatory Targets after Aneurysmal Subarachnoid Hemorrhage

“…and chemokines (MCP-1, MIP-1β, and CCL5) acting through their receptors and various adhesion molecules expressed on the surface of endothelial cells and infiltrating leukocytes, are also targets of modulation [ 27 ]. Various cellular targets, such as depletion of neutrophils or monocytes/macrophages, also downregulate inflammation [ 28 , 29 , 30 ]. Moreover, promoting microglial M2 polarization can afford neuroprotection after SAH [ 31 ].…”