Electron microscopy of the blood-brain barrier in disease

The anatomical site of the blood-brain barrier (BBB) is at the capillary endothelium mainly, with some contribution from astrocytes. Electron microscopic observations of endothelial cells and perivascular astrocytes comprising the BBB in brain edema and other pathological conditions are reviewed in this article. The tight junctions of cerebral endothelial cells open under several conditions such as infusion of hyperosmolar solutions. Pinocytotic vesicles increase under various pathological conditions and fenestrae appear in blood vessels of certain brain tumors and several non-neoplastic lesions. Inflammatory cells penetrate between or through endothelial cells. In long standing lesions, endothelial cells containing various tubular structures such as Weibel-Palade bodies proliferate. Other alterations include surface infoldings of endothelial cells and fluid diffusion through damaged endothelium. Astrocytic alterations include abnormal junctions between astrocytic processes in certain gliomas. In vivo and in vitro studies suggest that astrocytes maintain or develop certain functions of BBB. As the BBB is disrupted, edema fluid infiltrates the brain parenchyma. Because the white matter consists of nerve fibers without demonstrable junctions, it invades between nerve fibers. In the gray matter, expansion of the fluid is limited by complicated anatomical structures. In myelinated nerve fibers, edema fluid accumulates in five separate compartments of extracellular space.