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Repurposing Pharmaceuticals as Neuroprotective Agents for Cerebral Malaria

机译：Repurposing Pharmaceuticals as Neuroprotective Agents for Cerebral Malaria

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Background: Cerebral malaria (CM) is a severe complication of Plasmodium falciparuminfection which may result in death or developmental disability. The pathologic processes leadingto CM are not fully elucidated; however, widely accepted mechanisms include parasite sequestration,release of infected red blood cell contents, activation of endothelial cells, increased inflammatoryresponses, and ultimately dysfunction of the neurovascular unit (NVU). The endotheliumplays a central role in these processes as the site of parasitized erythrocyte sequestration and as theregulator of fluid extravasation into the central nervous system. Modulating endothelial barrierfunction at the NVU may provide new therapeutic approaches to improve outcomes in CM.Methods: Here we provide a narrative review of the literature of peer-reviewed research relatingto adjunctive therapies for CM. We discuss regulatory pathways of the NVU, with a focus on thepotential for pharmacologic modulation of the NVU to improve CM outcomes.Results: Recently licensed pharmaceuticals, developed as therapies for cancer or neurologicdisease, could be re-purposed for use as host-directed therapies in CM to target pathways involvedin endothelial stability and activation.Conclusion: The findings of this review highlight recently licensed pharmaceuticals that may bedeveloped as future adjunctive therapies for CM.

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