Abstract
Perivascular macrophages (PVMs) constitute a subpopulation of resident macrophages in the central nervous system (CNS). They are located at the blood-brain barrier and can contribute to maintenance of brain functions in both health and disease conditions. PVMs have been shown to respond to particle substances administered during the prenatal period, which may alter their phenotype over a long period. We aimed to investigate the effects of maternal exposure to ultrafine carbon black (UfCB) on PVMs and astrocytes close to the blood vessels in offspring mice. Pregnant mice were exposed to UfCB suspension by intranasal instillation on gestational days 5 and 9. Brains were collected from their offspring at 6 and 12 weeks after birth. PVM and astrocyte phenotypes were examined by Periodic Acid Schiff (PAS) staining, transmission electron microscopy and PAS-glial fibrillary acidic protein (GFAP) double staining. PVM granules were found to be enlarged and the number of PAS-positive PVMs was decreased in UfCB-exposed offspring. These results suggested that in offspring, “normal” PVMs decreased in a wide area of the CNS through maternal UfCB exposure. The increase in astrocytic GFAP expression level was closely related to the enlargement of granules in the attached PVMs in offspring. Honeycomb-like structures in some PVM granules and swelling of astrocytic end-foot were observed under electron microscopy in the UfCB group. The phenotypic changes in PVMs and astrocytes indicate that maternal UfCB exposure may result in changes to brain blood vessels and be associated with increased risk of dysfunction and disorder in the offspring brain.
Highlights
Resident phagocytes of the central nervous system (CNS) are categorized into four types: microglia, meningeal macrophages, choroid plexus macrophages, and perivascular macrophages (PVMs)
glial fibrillary acidic protein (GFAP)-positive astrocytes were not observed at any sites attached to blood vessels with PVMs with small Periodic Acid Schiff (PAS)-positive granules (Figure 7A), but were found at blood vessels with PVMs that had enlarged PAS-positive granules in the ultrafine carbon black (UfCB)-exposed offspring
We examined the effect of maternal exposure to UfCB on PVMs and surrounding tissue in murine CNS using PAS staining, transmission electron microscopy and GFAP immunohistochemistry
Summary
Resident phagocytes of the central nervous system (CNS) are categorized into four types: microglia, meningeal macrophages, choroid plexus macrophages, and perivascular macrophages (PVMs). PVMs are localized in the perivascular space (Virchow-Robin space) and are surrounded by the vascular endothelial basement membrane and glia limitans [4,5] In this space, PVMs adjoin endothelial cells, pericytes [4,5,6], and the end-foot of astrocytes, which are one of the types of cerebral parenchyma glial cells in the surrounding brain microvessels [7,8]. PVMs adjoin endothelial cells, pericytes [4,5,6], and the end-foot of astrocytes, which are one of the types of cerebral parenchyma glial cells in the surrounding brain microvessels [7,8] This space plays a important role in the drainage of interstitial fluid containing unnecessary substances and waste including b-amyloid from the central grey matter and cerebral cortex [9,10,11,12]. Because of their unique localization, phagocytic function and character PVMs are essential for maintaining blood brain barrier (BBB) function [15]
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