Other potential candidate molecules that may involve in the BMEC transcytosis can be secretory aspartyl proteinases SAP1-SAP9 of C. albicans (Ibrahim et al., 1998; Naglik et al., 1999). Cryptococcus neoformans can traverse BMECs without any obvious change in their integrity.

Transmission and scanning electron microscopy has revealed that C. neoformans induces the formation of microvilli-like protrusions to initiate entry into BMECs. These findings indicate that C. neoformans uses a transcellular mechanism (Chang et al., 2004). Very recent finding (Huang et al., 2011) unfolds cryptococcal invasion via lipid raft – endocytic pathway. CD44 molecules from lipid rafts see more can directly interact with hyaluronic acid of C. neoformans. The lipid raft molecule, ganglioside GM1, colocalizes with CD44 on the plasma membrane to which C. neoformans can adhere. Upon adhesion, cryptococci are internalized into the BMECs along with GM1 through vesicular structures. Apart from CD44, this endocytosis process is dependent on microtubule cytoskeleton and intracellular kinase-DYRK3 (dual-specificity tyrosine-phosphorylation-regulated kinase 3). Histoplasma capsulatum is able to invade CNS via surface protein Yps3p. This

protein is expressed as secretory protein in infected cells and may have a regulatory role in fungal transition and pathogenicity. Yps3p triggers TLR2 signaling BGB324 manufacturer and leads to the activation of NF-κB in microglial cells (Bohse & Woods, 2005) (Table 1). Plasmodium falciparum erythrocyte membrane protein (PfEMP-1)

mediates endothelial binding and affects barrier integrity. PfEMP-1 binds to ICAM-1, CD36, chondroitin sulfate, and other trypsin-sensitive binding determinants (Tripathi et al., 2007). Pathogen matures in parasitized red blood cells, which get attached to BMECs. This process is mediated by specific molecular adhesive events. This binding is not solely static but MYO10 can be a rolling interaction, similar to the early rolling that allows subsequent leukocyte tethering to ECs during physiological responses to inflammatory stimuli (Cooke et al., 1994). The ability of trypanosomes to invade the brain and induce an inflammatory reaction is well recognized. Process of trypanosomal traversal across the human BBB requires the participation of a PAR-2-mediated calcium signaling pathway. Work of Grab and his colleagues (Grab et al., 2004) shows that Trypanosoma translocates BBB by generating Ca2+ activation signals by parasite cysteine proteases. Trypanosomal cathepsin (brucipain) can initiate BBB translocation and increases vascular permeability by interaction with host G protein-coupled receptors (Abdulla et al., 2008). The mechanism by which Acanthamoeba transmigrates the BBB is the most complex and may involve both pathogen (adhesins, proteases and phospholipases) and host factors (IL-β, IL-α, TNF-α, IFN-γ, and host cell apoptosis).