Immunoultrastructural expression of intercellular adhesion molecule-1 in endothelial cell vesiculotubular structures and vesiculovacuolar organelles in blood-brain barrier development and injury

Blood vessels from the vasculature of mouse brains during postnatal development and from human brain tumors (hemangiomas) removed at biopsy were examined immunocytochemically by transmission electron microscopy (TEM) or high-voltage transmission electron microscopy (HVEM) to determine the expression of intercellular adhesion molecule-1 (ICAM-1). In the mouse brains, ICAM-1 was shown to be initially expressed on the luminal and abluminal endothelial cell (EC) surfaces on day 3 after birth. ICAM-1 intensity increased on the luminal EC surfaces and labeled vesiculotubular profiles (VTS, defined in the present report) between days 5 and 7. After 2 weeks and at 6 months after birth, ICAM-1 labeling was weak or absent on the luminal EC surfaces. The hemangiomas presented a strong ICAM-1 reaction product on the luminal EC surfaces of small and large blood vessels associated with the VTS, with a weaker labeling of the abluminal or adventitial aspects of larger blood vessels. TEM of vesiculovacuolar structures (VVOs) within ECs from arteries and veins also demonstrated reaction product for ICAM-1 labeling. Three-dimensional stereo-pair images in the HVEM enhanced the visualization of gold particles that were attached to the inner-delimiting membrane surfaces of EC VTS, and VVOs, respectively. These observations raise the possibility that the neonatal leukocytes and tumor cells may utilize these endothelial structures as a route across the developing and injured blood-brain barrier (BBB).