The perivascular astroglial sheath provides a complete covering of the brain microvessels: An electron microscopic 3D reconstruction

Abstract

The unravelling of the polarized distribution of AQP4 in perivascular astrocytic endfeet has revitalized the interest in the role of astrocytes in controlling water and ion exchange at the brain-blood interface. The importance of the endfeet is based on the premise that they constitute a complete coverage of the vessel wall. Despite a number of studies based on different microscopic techniques this question has yet to be resolved. We have made an electron microscopic 3D reconstruction of perivascular endfeet in CA1 (stratum moleculare) of rat hippocampus. The endfeet interdigitate and overlap, leaving no slits between them. Only in a few sites do processes--tentatively classified as processes of microglia--extend through the perivascular glial sheath to establish direct contact with the endothelial basal lamina. In contrast to the endfoot covering of the endothelial tube, the endfoot covering of the pericyte is incomplete, allowing neuropil elements to touch the basal lamina that enwraps this type of cell. The 3D reconstruction also revealed large bundles of mitochondria in the endfoot processes that came in close apposition to the perivascular endfoot membrane. Our data support the idea that in pathophysiological conditions, the perivascular astrocytic covering may control the exchange of water and solutes between blood and brain and that free diffusion is limited to narrow clefts between overlapping endfeet.

Critical role of aquaporin-4 (AQP4) in astrocytic Ca 2+ signaling events elicited by cerebral edema

“…These data are consistent with a number of studies suggesting that aquaporin-4 (AQP4) serves as a primary influx route for water from blood to brain (2,3). AQP4 is strongly expressed in astrocytic endfeet (4), which form a continuous pericapillary sheath that is interrupted only by a narrow extracellular space (5).…”

Fine processes of Nestin-GFP–positive radial glia-like stem cells in the adult dentate gyrus ensheathe local synapses and vasculature

“…Astrocytes of the ML of the dentate gyrus and other regions of the hippocampus can position their cell bodies directly adjacent to blood vessels, completely enclosing large sections of a vessel (41,42). However, in the vicinity of an NGPα RGL stem cell process emerging from the GCL, astrocytic coverage of the blood vessel was not always complete; the two types of process shared coverage of the blood vessel (Fig.…”

Strategies for immunohistochemical protein localization using antibodies: What did we learn from neurotransmitter transporters in glial cells and neurons

“…A plasma membrane is about 5 nm thick and the width of the extracellular space (the distances between neighboring cellular extensions) is typically in the range 20-40 nm, while the diameter of a glutamate transporter trimer is believed to be about 8 nm (Yernool et al, 2004). Cellular elements are tightly intermingled (Kirov et al, 1999;Sorra and Harris, 2000;Witcher et al, 2010;Harris and Weinberg, 2012;Mathiisen et al, 2010). This is schematically illustrated in figure 8.…”