From the Research
Cerebral malaria develops through a complex cascade of events triggered by Plasmodium falciparum infection, involving the sequestration of infected red blood cells in cerebral blood vessels, inflammatory responses, and damage to the blood-brain barrier, ultimately leading to neuronal dysfunction and high mortality rates 1. The process begins when infected red blood cells adhere to the endothelial lining of cerebral blood vessels through parasite proteins like PfEMP1 binding to receptors such as ICAM-1 and CD36. This sequestration causes microvascular obstruction, reducing cerebral blood flow and oxygen delivery.
- The adherent parasitized cells also trigger inflammatory responses, with increased production of cytokines like TNF-α, IL-1β, and IFN-γ, which damage the blood-brain barrier 2.
- As the barrier integrity fails, plasma proteins leak into brain tissue, causing cerebral edema.
- Additionally, platelets aggregate at sites of endothelial activation, further compromising circulation. The combination of reduced perfusion, inflammation, metabolic disturbances, and oxidative stress leads to neuronal dysfunction and the clinical manifestations of cerebral malaria, including altered consciousness, seizures, and coma.
- The breakdown of the blood-brain barrier also allows direct contact between parasites and neural tissue, potentially causing direct neurotoxicity 2. This multifaceted pathophysiology explains why cerebral malaria has such high mortality rates and why survivors often experience long-term neurological sequelae, as noted in a recent study published in the Frontiers in cellular and infection microbiology 1. The current understanding of cerebral malaria pathogenesis highlights the need for effective treatments to prevent long-term neurological sequelae and reduce mortality rates, with artesunate being a preferred treatment option 3.