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Trypanosoma brucei is one of the protozoa parasites that can enter the brain and cause injury associated with toxic effects of parasite-derived molecules or with immune responses against infection. Other protozoa parasites with brain tropism include Toxoplasma, Plasmodium, Amoeba , and, eventually, other Trypanosomatids such as T. cruzi and Leishmania . Together, these parasites affect billions of people worldwide and are responsible for more than 500.000 deaths annually. Factors determining brain tropism, mechanisms of invasion as well as processes ongoing inside the brain are not well understood. But, they depend on the parasite involved. The pathogenesis caused by T. brucei initiates locally in the area of parasite inoculation, soon trypanosomes rich the blood, and the disease enters in the so-called early stage. The pathomechanisms in this phase have been described, even molecules used to combat the disease are effective during this period. Later, the disease evolves towards a late-stage, characterized by the presence of parasites in the central nervous system (CNS), the so-called meningo-encephalitic stage. This phase of the disease has not been sufficiently examined and remains a matter of investigation. Here, I stress the importance of delve into the study of the neuropathogenesis caused by T. brucei , which will enable the identification of pathways that may be targeted to overcome parasites that reached the CNS. Finally, I highlight the impact that the application of tools developed in the last years in the field of neuroscience will have on the study of neglected tropical diseases.

Neuropathogenesis caused by Trypanosoma brucei, still an enigma to be unveiled