PT - JOURNAL ARTICLE AU - Hackett, Mark J. AU - Aitken, Jade B. AU - El-Assaad, Fatima AU - McQuillan, James A. AU - Carter, Elizabeth A. AU - Ball, Helen J. AU - Tobin, Mark J. AU - Paterson, David AU - de Jonge, Martin D. AU - Siegele, Rainer AU - Cohen, David D. AU - Vogt, Stefan AU - Grau, Georges E. AU - Hunt, Nicholas H. AU - Lay, Peter A. TI - Mechanisms of murine cerebral malaria: Multimodal imaging of altered cerebral metabolism and protein oxidation at hemorrhage sites AID - 10.1126/sciadv.1500911 DP - 2015 Dec 01 TA - Science Advances PG - e1500911 VI - 1 IP - 11 4099 - http://advances.sciencemag.org/content/1/11/e1500911.short 4100 - http://advances.sciencemag.org/content/1/11/e1500911.full SO - Sci Adv2015 Dec 01; 1 AB - Using a multimodal biospectroscopic approach, we settle several long-standing controversies over the molecular mechanisms that lead to brain damage in cerebral malaria, which is a major health concern in developing countries because of high levels of mortality and permanent brain damage. Our results provide the first conclusive evidence that important components of the pathology of cerebral malaria include peroxidative stress and protein oxidation within cerebellar gray matter, which are colocalized with elevated nonheme iron at the site of microhemorrhage. Such information could not be obtained previously from routine imaging methods, such as electron microscopy, fluorescence, and optical microscopy in combination with immunocytochemistry, or from bulk assays, where the level of spatial information is restricted to the minimum size of tissue that can be dissected. We describe the novel combination of chemical probe–free, multimodal imaging to quantify molecular markers of disturbed energy metabolism and peroxidative stress, which were used to provide new insights into understanding the pathogenesis of cerebral malaria. In addition to these mechanistic insights, the approach described acts as a template for the future use of multimodal biospectroscopy for understanding the molecular processes involved in a range of clinically important acute and chronic (neurodegenerative) brain diseases to improve treatment strategies.