This results of this study highlight the apparent inconsistency between the trypanosome burden in the brain and the degree of BBB impairment as evidenced by the severity of the neuroinflammatory reaction present within the brain of trypanosome infected animals. Although statistical differences between the neuropathology scores were apparent between the groups of mice examined through the various stages of disease progression the neuroinflammatory response remained mild to moderate throughout with no inflammatory cells infiltrating the neuropil. This suggests that the mechanisms in place within the brain to control the inflammatory response and maintain homeostasis remain largely effective despite the barrier dysfunction and the increasing parasite burden. Furthermore, the neuroanatomical expression patterns of tight junction proteins and adhesion molecules differ between the BBB, the blood-meningeal barrier and the blood-CSF barrier . This could result in differential infiltration of specific regions dependent on the particular immune environment. Several host and parasite factors have been implicated as key determinants of disease progression. These include molecules regulating both the innate and adaptive immune response. For example, Toll-like receptor (TLR) 2- and TLR9- MyD88 signalling have been shown to stimulate the expression of inflammatory mediators such as TNF-α and IFN α/β which initiate leucocyte and parasite transmigration into the CNS  and additional inflammatory mediators such as IFN-γ ,  and CXCL10  have also been shown to play a vital role in this process. Furthermore, the migration of leucocytes across the BBB as well as the laminin subtype composition of the basement membrane, influence the ability of trypanosomes to enter the CNS ,  and increased levels of ICAM and E-selectin have been demonstrated following infection . Other non-immune molecules such as matrix metalloproteases , and parasite cysteine proteases  also appear to affect BBB penetration by the parasites.