Anatomical relationships of the pia mater to cerebral blood vessels in man

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✓ Using scanning and transmission electron microscopy and light microscopy, the authors studied the human pia mater and its relationship to the entry of blood vessels into the normal cerebral cortex. The purpose of this investigation was to examine the long-established concept that the subarachnoid space communicates directly with the perivascular spaces of the cerebral cortex. Brains obtained post mortem from subjects with recent subarachnoid hemorrhage (SAH) and purulent leptomeningitis were studied by light microscopy to determine the permeability of the pia mater to red blood cells and inflammatory cells. Scanning electron microscopy showed that the normal pia mater is a flat sheet of cells that is reflected from the surface of the brain to form the outer coating of the meningeal vessels in the subarachnoid space. Transmission electron microscopy confirmed that the cells of the pia mater are joined by junctional complexes and form a continuous sheet that separates the subarachnoid space on one side from the subpial and perivascular spaces on the other. Thus, neither the pia mater nor the subarachnoid space extends into the brain beside blood vessels as they enter the cerebral cortex. The perivascular spaces were, in fact, found to be confluent with the subpial space and not with the subarachnoid space. In cases of recent SAH, red blood cells did not enter the perivascular spaces from the subarachnoid space; neither did India ink injected post mortem into the subarachnoid space pass into the perivascular spaces. The results of these crude tracer studies suggest that the pia mater is an effective barrier to the passage of particulate matter. Histological examination of brains of patients who had died with purulent leptomeningitis showed that inflammatory cells were present in the cortical perivascular spaces and in the contiguous subpial spaces. The presence of a large number of inflammatory cells in the subarachnoid space suggests that inflammatory cells readily penetrate the pia mater that separates the perivascular spaces from the subarachnoid space. The permeability of the pia mater to small molecular weight substances is briefly discussed.

Article Information

Address reprint requests to: Roy O. Weller, M.D., Department of Pathology (Neuropathology), Level E, South Laboratory and Pathology Block, Southampton General Hospital, Southampton SO9 4XY, England.

© AANS, except where prohibited by US copyright law.

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Figures

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    Scanning electron micrograph of a normal cerebral sulcus, transverse cut. The outer layer of arachnoid (A) can be seen lying horizontally across the top of the figure. Sheets of pia (p) on the lateral walls of the sulcus are partly detached from the underlying cortex. A subarachnoid vessel in the center of the figure is attached to the arachnoid by thin chordae and broader trabeculae. × 28.

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    Scanning electron micrograph of the lateral wall of a normal cerebral sulcus. An artery in the subarachnoid space is seen spreading its branches over the sheet-like pia mater (pia). As branches of the artery disappear from view, the outer leptomeningeal coat of the vessel fuses with the pia mater as a fan-like structure (black arrow). A vessel branch in the center of the picture appears to pass into a deep hole (open arrow), which is probably an invagination of the pia. Thin chordae run between the pia and vessels, × 100.

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    Higher-power scanning electron micrograph of the vessel entry zone as shown by the black arrow in Fig. 2. The pia mater forms a fan-like structure as it is reflected onto the surface of the artery. A thin chorda is seen at the left of the picture, × 400.

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    Upper Left: Transmission electron micrograph (TEM) showing the entry zone of a small blood vessel at the surface of normal cerebral cortex. A continuous layer of pia mater (p) separates the subarachnoid space (SAS) from the subpial space (SPS). As the vessel enters the cortex, the subpial space extends along the outside of the vessel as the perivascular space (long arrows). × 2200. Upper Right: Higher-power TEM of the region marked by the lower of the two long arrows in upper left. The irregular surface of the cortical glia limitans can be seen at the bottom of the figure, and its basement membrane is separated from the vessel wall by the subpial-perivascular spaces (SPS-PVS) containing sparse collagen fibers. × 10,700. Lower: Higher-power TEM of the pia mater. Thin cell processes partly coated by a structure similar to basement membrane (b) separate the subarachnoid space (SAS) from the subpial space (SPS). The intercellular junctions (j) are also shown, × 33,150.

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    Photomicrograph following India ink injection into the cerebrospinal fluid of normal brain. There is a funnellike invagination of the subarachnoid space (SAS) by the ink but no penetration of the perivascular space as the vessel enters the cortex. The brain is artifactually retracted from the vessel. H & E, × 300.

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    Photomicrograph of a specimen from a subject who died after subarachnoid hemorrhage. Red blood cells (seen black) fill the subarachnoid space at the top of the figure and the lumen of the cortical vessel in the center but have not entered the barely visible perivascular space (ps). The artifactual space (as) between the vessel and the brain is not the true perivascular space. Diaminobenzidine and hematoxylin, × 300.

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    Photomicrographs of a specimen from a subject who died of leptomeningitis. Gordon and Sweet reticulin stain. Left: Inflammatory cells fill the subarachnoid space (SAS) and separate the arachnoid coating (A) from subarachnoid vessels. Connective tissue of the pia mater (p) is separated from the basement membrane of the glia limitans (b) by the subpial space. A vessel enters the cortex in the lower left portion of the figure. × 300. Center: A branch from a large subarachnoid vessel at the top of the figure enters the cortex. The pia mater (p) fuses with the outer coating of the vessel. Subpial inflammatory cells separate the pia mater from the basement membrane of the glia limitans (b). × 300. Right: As the vessel in the center of the figure enters the cortex, it is surrounded by a perivascular space (ps) that is expanded by inflammatory cells and is in continuity with the subpial space between the pia mater (p) and the basement membrane of the glia limitans (b). There are focal gaps in the pia mater. SAS = subarachnoid space, × 470.

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    Photomicrograph of a specimen from a subject who died of leptomeningitis. A vessel enters the cortex obliquely and is surrounded by the basement membrane of the glia limitans (b). The pia mater (p) separates the subarachnoid space at the top of the figure from the subpial and perivascular spaces below. Gordon and Sweet reticulin stain, × 470.

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    Diagrammatic representations of the relationship between the subarachnoid and perivascular spaces in man. The diagrams are based on data derived from this study and show the relationship in normal brain (A), in the brain of patients who died of subarachnoid hemorrhage (B), and in the brain of patients who died of leptomeningitis (C).

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