MRI demonstrates glutamine antagonist-mediated reversal of cerebral malaria pathology in mice
Abstract
Cerebral malaria (CM) is the deadliest complication of Plasmodium falciparum infection, resulting in a 15 to 25% mortality rate in African children despite antimalarial chemotherapy. Tragically, nearly a fourth of pediatric CM survivors suffer long-term neurological sequelae. There is an urgent public health and humanitarian need for therapies for CM. In a mouse model of CM, we used magnetic resonance imaging (MRI) to monitor infected mice longitudinally as CM progressed and noninvasively demonstrate that the edema and blood-brain barrier dysfunction, which ultimately result in death, are rapidly reversed by treatment with the glutamine antagonist JHU-083. The similarities between CM MRI shown in mice and those reported in children and adults suggest that glutamine antagonists may be effective CM therapies.
- Publication:
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Proceedings of the National Academy of Science
- Pub Date:
- December 2018
- DOI:
- 10.1073/pnas.1812909115
- Bibcode:
- 2018PNAS..11512024R