Cerebral malaria: attenuating brain injury and mortality with neuregulin-1

Cerebral malaria (CM) is the most severe neurological complication of infection with Plasmodium falciparum. Over 575,000 cases are reported annually and children in sub-Saharan Africa are the most affected. A subset of survivors develops neurological, behavioral and cognitive deficits. Cerebral malaria is characterized by the sequestration of Plasmodium falciparum-infected erythrocytes (pRBC), increased circulating free heme, inflammation, brain swelling, vascular dysfunction and brain tissue injury.

The pathogenesis of CM associated neuro-cognitive sequelae is poorly understood: coma develops through multiple mechanisms and several mechanisms may mediate the accompanying brain injury – how an intravascular parasite causes brain injury remains misunderstood. Understanding the injury and repair processes in infected hosts is important to develop appropriate neuro-protective interventions. Recent studies have identified NRG-1, an 8 kDa secreted cytoprotective trophic factor, encoded by the neuregulin/NRG-1 gene located on the short arm of chromosome 8 [4], which mediates injury/repair mechanisms in stroke [1], cardiovascular diseases [2] and tumors [3] in addition to attenuating experimental cerebral malaria (ECM) in a murine model.