Neuronal Damage in Murine Experimental Cerebral Malaria, Implications for Neuronal Repair and Sequelae

TL;DR

This study explores neuronal damage and potential repair mechanisms in a mouse model of cerebral malaria, focusing on the hippocampus and its long-term effects.

Contribution

The study reveals extensive neuronal damage in murine cerebral malaria and identifies potential repair responses involving neuroprogenitor cells.

Findings

Plasmodium infection causes significant neuronal damage in the hippocampus of eCM mice.

Neurofilament light chain levels increase in cerebrospinal fluid during eCM, indicating neuronal fragmentation.

Increased influx of neuroprogenitor cells suggests a potential repair mechanism in eCM.

Abstract

Cerebral malaria (CM) is a deadly complication of P. falciparum infection. Although adults with CM have a higher mortality rate, CM affects mostly children under the age of 5 years. Neurological symptoms and signs include impaired consciousness, coma, seizures, and increased intracranial hypertension. Upon survival of a CM episode, persistent neurologic deficits occur in a subset of surviving children. These sequelae include recurrent seizures, behavioral deficits, loss of developmental milestones, learning disabilities and attention deficit hyperactivity disorder, which can remain with the survivors. The underlying neuropathology of these post CM neurologic sequelae are unclear. Therefore, we probed the extensive neuronal damage that occurs in an experimental murine model of cerebral malaria (eCM), focusing on the hippocampus. In addition, we explored responses of neuro-progenitor cells (NPC’s) and potential repair mechanisms. We report here that Plasmodium infection causes extensive neuronal damage in the hippocampus, characterized by a loss of neuronal NeuN and double cortin (DCX) immunostaining in eCM mice. On day 6 of eCM we also observed increased neurofilament light chain staining, indicative of neuronal fragmentation, which was accompanied by an increase in neurofilament light chain in CSF but not seen in plasma. A concomitant increase in the influx of neuroprogenitor cells in eCM was observed, suggesting ongoing neuronal repair.

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