Separation of the perivascular basement membrane provides a conduit for inflammatory cells in a mouse spinal cord injury model

Abstract

Spinal cord injury results in disruption of the cord microstructure, which is followed by inflammation leading to additional deterioration. Perivascular basement membranes are a component of the spinal cord microstructure that lies between blood vessels and astrocytes. The impact of disrupting the basement membrane structure on the expansion of inflammation has not been fully examined. The objective of this study was to clarify the relationship between damage to basement membranes and inflammation after spinal cord injury. Immunohistochemical analyses of the perivascular extracellular matrix were performed in a mouse spinal cord injury model. In normal tissue, the perivascular basement membrane was a single-layer structure produced by both endothelial cells and surrounding astrocytes. After spinal cord injury, however, the perivascular basement membrane often separated into an inner endothelial basement membrane and an outer parenchymal basement membrane. The altered basement membranes formed during the acute phase (within 7 days after spinal cord injury). During the subacute phase of injury, numerous monocytes and macrophages accumulated in the space between the separated basement membranes and infiltrated into the parenchyma where astrocytic endfeet were displaced. Infiltration of inflammatory cells from the injury core was attenuated coincident with the appearance of the glia limitans and glial scar. Furthermore, the outer parenchymal basement membrane was connected to the basement membrane of the glia limitans surrounding the injury core. Our data suggest that structurally altered basement membranes facilitate expansion of secondary inflammation during the subacute phase of spinal cord injury.