""""""""Neural dysfunction and neuroinflammation in African brain disorders"""""""". Infectious diseases of the brain are among the most devastating brain disorders that plague developing countries. In spite of this, research on these diseases is mostly neglected in the neuroscience community of the """"""""North"""""""" of the world. It is therefore mandatory to strengthen the capacity for research in regions struck by these diseases, with a view to direct research to the needs in the field and increase the international awareness for collaborative research efforts. Several brain infections are lethal if left untreated, and treatments are often non-efficient, expensive or not readily available. Furthermore, such diseases cause neurological disabilities (epilepsy in cerebral malaria and neurocysticercosis, severe sleep disturbances in African trypanosomiasis and neuroAIDS and behavior changes in toxoplasmosis and rabies) and sequelae even after recovery from the acute illness.
The aim of the R21 exploratory project is to plan for capacity building for research on brain dysfunctions in inflammatory diseases which are prevalent in sub-Saharan Africa. The activities will be centered around the Medical Faculty at the University of Yaounde 1 in Cameroon. This country is located at the cross-road between West and Central Africa and could therefore serve as a center for the world region in which inflammatory brain disease is most prevalent. Two European laboratories with extensive experience to conduct research on these diseases will co-operate with a Cameroonian partner in this capacity building endeavor. The research planned for the R21 project is focused on brain involvement in human African trypanosomiasis (HAT) caused by the parasites Trypanosoma brucei (Tb), spread tsetse flies in sub- Saharan Africa.
The specific aim i s to correlate Tb passage into the brain across the blood-brain barrier (BBB) with changes of inflammatory molecules (cytokines and chemokines) in the brain and functional changes (alterations of the sleep pattern and rest-activity rhythm during 24h). The latter could be revealed in patients by a non-invasive strategy, namely actigraph recordings with relatively inexpensive wrist-worn watches. Monitoring of brain invasion by Tb is mandatory for therapeutic interventions, because this encephalitic stage requires treatment with very toxic drugs. However, diagnostic criteria for this stage are still ill-defined, and better methods to diagnose and monitor the diseases are urgently needed. The needs will be assessed for research on other brain infections, prevalent in the region, which clinically present with neurological dysfunctions including epilepsy, sleep disruptions and behaviour changes .This platform for inflammatory brain disorder research projects will then have the potentials to be accessible to researchers in West and Central Africa countries
Infections of the nervous system affect large numbers of children and adults, especially in developing countries, causing inflammation of the brain and neurological disabilities or death. Most of these diseases are neglected because they affect the """"""""South"""""""" of the world, but they also have an impact on countries of the """"""""North"""""""", and research on these diseases can open new perspectives in brain sciences. This project proposes pilot studies on one of these neglected diseases, sleeping sickness, and a plan to strengthen research capacity in African countries in which infectious diseases are endemic.
|Kristensson, Krister; Masocha, Willias; Bentivoglio, Marina (2013) Mechanisms of CNS invasion and damage by parasites. Handb Clin Neurol 114:11-22|
|Amin, Daniel Ndem; Vodnala, Suman K; Masocha, Willias et al. (2012) Distinct Toll-like receptor signals regulate cerebral parasite load and interferon ?/? and tumor necrosis factor ?-dependent T-cell infiltration in the brains of Trypanosoma brucei-infected mice. J Infect Dis 205:320-32|
|Njamnshi, Alfred K; Seke Etet, Paul F; Perrig, Stephen et al. (2012) Actigraphy in human African trypanosomiasis as a tool for objective clinical evaluation and monitoring: a pilot study. PLoS Negl Trop Dis 6:e1525|
|Masocha, Willias; Kristensson, Krister (2012) Passage of parasites across the blood-brain barrier. Virulence 3:202-12|
|Seke Etet, Paul F; Palomba, Maria; Colavito, Valeria et al. (2012) Sleep and rhythm changes at the time of Trypanosoma brucei invasion of the brain parenchyma in the rat. Chronobiol Int 29:469-81|
|Bentivoglio, Marina; Mariotti, Raffaella; Bertini, Giuseppe (2011) Neuroinflammation and brain infections: historical context and current perspectives. Brain Res Rev 66:152-73|