Unfolding evolving pathology in experimental cerebral malaria model treated with artesunate with in vivo MRI

Motivation: Artesunate is the first-line treatment of P. falciparum malaria. However, despite artesunate therapy, there is a 15% fatality rate in severe malaria and survivors can suffer long-term neurocognitive deficits. Goal(s): Describe the evolving pathology in experimental cerebral malaria (ECM) model treated with artesunate, to develop a model for testing adjunctive therapy in cerebral malaria. Approach: In vivo MRI was applied on ECM mice prior to and post artesunate treatment. Results: Despite rapid clearance of the parasite by artesunate, significantly reduced CBF and subsequent reperfusion/reoxygenation injury is detected by MRI, and may ultimately cause neurocognitive deficits in CM survivors. Impact: It is critical to understand the evolving pathology after antimalarial cure with artesunate in cerebral malaria in order to design effective adjunctive therapy, to reduce mortality and neurocognitive impairment. Reduced CBF and its rapid recovery may contribute to CM neuropathology.