Mechanism Of The Cryptococcus Neoformans Penetrating The Brain Microvascular Endothelial Cell Of Blood-Brain Barrier And Its Effect To The Central Nervous System

[Background] The integrity of the brain microvascular endothelial cells (BMEC) of the blood-brain barrier (BBB) is destroyed by apoptosis and opened tight junction, which lead increasing of permeability of BBB. [Objective] To explore the mechanism of the cryptococcus neoformans (C.neoformans) penetrating the BMEC of BBB and observe its effect on the central nervous system (CNS). [Method] We established both in vitro model of the BBB and in vivo mouse model to investigate the C.neoformans association with and traversal of the BBB. Transmission electron microscope, scanning electron microscope, flow cytometry, flourescence immunocytochemistry, immunity chemical chemistry, etc. were used in this experiment. [Result] Exposure of human umbilical vein endothelial cells (HUVEC) to C.neoformans triggered the formation of microvillus-like membrane protrusions within 2 to 12 h. C.neoformans adhered to and were internalized by the HUVEC. The histopathology of mouse brains obtained after vena caudalis injection of C. neoformans showed that the C.neoformans escaped from the brain capillary vessels into the brain parenchyma by 6 h. Apoptosis of BMEC and opened tight junction of BBB led increasing of permeability of BBB. [Conclusion] Our findings indicate that the mechanism of C.neoformans invade the central nervous system by crossing the endothelium of the BBB is (1) transmembrane function of C.neoformans; (2) opened tight junction of BMEC; (3) apoptosis of BMEC; (4) related cellular factors which make the permeability of endothelial cell increased.