Mechanisms of murine cerebral malaria: multimodal imaging of altered cerebral metabolism and protein oxidation at hemorrhage sites

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dc.contributor.authorHackett, MJen_AU
dc.contributor.authorAitken, JBen_AU
dc.contributor.authorEl-Assaad, Fen_AU
dc.contributor.authorMcQuillan, JAen_AU
dc.contributor.authorCarter, EAen_AU
dc.contributor.authorBall, HJen_AU
dc.contributor.authorTobin, MJen_AU
dc.contributor.authorPaterson, DJen_AU
dc.contributor.authorde Jonge, MDen_AU
dc.contributor.authorSiegele, Ren_AU
dc.contributor.authorCohen, DDen_AU
dc.contributor.authorVogt, Sen_AU
dc.contributor.authorGrau, GEen_AU
dc.contributor.authorHunt, NHen_AU
dc.contributor.authorLay, PAen_AU
dc.date.accessioned2022-02-07T04:15:41Zen_AU
dc.date.available2022-02-07T04:15:41Zen_AU
dc.date.issued2015-12-18en_AU
dc.date.statistics2022-02-04en_AU
dc.description.abstractUsing 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. 2015 © The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. Distributed under a Creative Commons Attribution Non Commercial Licence 4.0 (CC BY-NC).en_AU
dc.identifier.articlenumbere1500911en_AU
dc.identifier.citationHackett, M. J., Aitken, J. B., El-Assaad, F., McQuillan, J. A., Carter, E. A., Ball, H. J., Tobin, M, J., Paterson, D., de Jonge, M. D., Siegele, R., Cohen, D. D., Vogt, S., Grau, G. E., Hunt, N. H. & Lay, P. A. (2015). Mechanisms of murine cerebral malaria: multimodal imaging of altered cerebral metabolism and protein oxidation at hemorrhage sites. Science Advances 1(11), e1500911. doi://10.1126/sciadv.1500911en_AU
dc.identifier.issn2375-2548en_AU
dc.identifier.issue11en_AU
dc.identifier.journaltitleScience Advancesen_AU
dc.identifier.urihttps://www.science.org/doi/full/10.1126/sciadv.1500911en_AU
dc.identifier.urihttps://apo.ansto.gov.au/dspace/handle/10238/12792en_AU
dc.identifier.volume1en_AU
dc.language.isoenen_AU
dc.publisherAmerican Association for the Advancement of Scienceen_AU
dc.subjectMalariaen_AU
dc.subjectCerebral cortexen_AU
dc.subjectBrainen_AU
dc.subjectInjuriesen_AU
dc.subjectPathologyen_AU
dc.subjectMicroscopyen_AU
dc.subjectFluorescenceen_AU
dc.subjectQuantitative chemical analysisen_AU
dc.subjectPathogenesisen_AU
dc.titleMechanisms of murine cerebral malaria: multimodal imaging of altered cerebral metabolism and protein oxidation at hemorrhage sitesen_AU
dc.typeJournal Articleen_AU
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