About this Research Topic
Cerebral malaria is a life-threatening complication of malarial disease caused by the parasite Plasmodium falciparum, with children the most affected population. It is responsible for approximately 90% of malaria deaths, and ~25% of patients who survive suffer from long-term neurological problems, including seizures and neurocognitive deficits that profoundly affect their quality of life.
The symptoms and signs of cerebral malaria are diverse in adults and children, ranging from fever, headache and irritability to agitation, delirium, seizures, vomiting and coma. The pathophysiology is also complex and age-dependent, involving sequestration of infected erythrocytes, cerebral inflammation, dysregulation of coagulation and endothelial dysfunction. The essential role of the blood-brain barrier (BBB) in this process is well known, but the precise underlying mechanisms of BBB disruption during cerebral malaria remain unclear. Studies in humans and mouse models have discovered several nonexclusive pathogenic mechanisms that are associated with disturbances of the BBB after the parasite infection: adhesion of infected red blood cells; release of pro-inflammatory cytokines; and cerebrovascular constriction due to an increased blood coagulation in the microvasculature. Moreover, activation of astrocytes and microglia has also been proposed to play a role through the regulation of cytokines and chemokines. Pericyte dysfunction has also been reported in cerebral malaria, pointing towards their role in maintaining the integrity of the BBB. A role for extracellular vesicles, notably microparticles, abnormal accumulation of metabolites and microRNAs has also been proposed.
Finally, recent reports have highlighted the effects of distant organ dysfunction on the brain in severe malaria, which has challenged our understanding of the concept of “cerebral” malaria. The BBB and gut barrier communicate with each other and with the environment through a complex network of interactions which may exacerbate microvascular lesions in cerebral malaria. Similarly, renal impairment has been associated with more severe brain damage in falciparum malaria, through a variety of pathogenic processes.
No specific or adjunctive treatment exists to treat cerebral malaria to date, so understanding the mechanisms involved in the disturbance of BBB integrity will facilitate the discovery of new therapeutic targets.
This Research Topic aims to collect the most recent knowledge about the mechanisms responsible for the breakdown of the BBB in cerebral malaria, with a wider focus on the role of distant organ involvement in severe falciparum infection, including liver, kidney, lung and gut dysfunction. We welcome all types of manuscripts (original research, review, minireviews, methods and perspectives) and encourage submissions covering, but not limited to, the following themes:
- New experimental models to study the disruption/remodeling of the BBB in cerebral malaria, such as organ-on-a-chip, organoid techniques, etc.
- Immune responses to malaria at the BBB
- BBB integrity in patients with long-term neurological conditions and role of distant organ dysfunction
- Biomarkers of BBB disruption and novel diagnostic/prognostic tools
- Repair mechanism in survivors and injury-reversal therapeutic strategies
The symptoms and signs of cerebral malaria are diverse in adults and children, ranging from fever, headache and irritability to agitation, delirium, seizures, vomiting and coma. The pathophysiology is also complex and age-dependent, involving sequestration of infected erythrocytes, cerebral inflammation, dysregulation of coagulation and endothelial dysfunction. The essential role of the blood-brain barrier (BBB) in this process is well known, but the precise underlying mechanisms of BBB disruption during cerebral malaria remain unclear. Studies in humans and mouse models have discovered several nonexclusive pathogenic mechanisms that are associated with disturbances of the BBB after the parasite infection: adhesion of infected red blood cells; release of pro-inflammatory cytokines; and cerebrovascular constriction due to an increased blood coagulation in the microvasculature. Moreover, activation of astrocytes and microglia has also been proposed to play a role through the regulation of cytokines and chemokines. Pericyte dysfunction has also been reported in cerebral malaria, pointing towards their role in maintaining the integrity of the BBB. A role for extracellular vesicles, notably microparticles, abnormal accumulation of metabolites and microRNAs has also been proposed.
Finally, recent reports have highlighted the effects of distant organ dysfunction on the brain in severe malaria, which has challenged our understanding of the concept of “cerebral” malaria. The BBB and gut barrier communicate with each other and with the environment through a complex network of interactions which may exacerbate microvascular lesions in cerebral malaria. Similarly, renal impairment has been associated with more severe brain damage in falciparum malaria, through a variety of pathogenic processes.
No specific or adjunctive treatment exists to treat cerebral malaria to date, so understanding the mechanisms involved in the disturbance of BBB integrity will facilitate the discovery of new therapeutic targets.
This Research Topic aims to collect the most recent knowledge about the mechanisms responsible for the breakdown of the BBB in cerebral malaria, with a wider focus on the role of distant organ involvement in severe falciparum infection, including liver, kidney, lung and gut dysfunction. We welcome all types of manuscripts (original research, review, minireviews, methods and perspectives) and encourage submissions covering, but not limited to, the following themes:
- New experimental models to study the disruption/remodeling of the BBB in cerebral malaria, such as organ-on-a-chip, organoid techniques, etc.
- Immune responses to malaria at the BBB
- BBB integrity in patients with long-term neurological conditions and role of distant organ dysfunction
- Biomarkers of BBB disruption and novel diagnostic/prognostic tools
- Repair mechanism in survivors and injury-reversal therapeutic strategies
Keywords: Cerebral malaria, pathogenesis, blood brain barrier (BBB), neurological deficits, therapeutic strategies
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.
