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Published on: January 2, 2013
Neuronal Damage in Murine Experimental Cerebral Malaria, Implications for Neuronal Repair and Sequelae
Monique F Stins1,2,3, Irene Gramaglia2, Joyce Velez2
1Malaria Research Institute, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
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.
Insights
Cerebral malaria (CM) causes significant neuronal damage in the hippocampus, particularly in children. Research in a mouse model indicates potential repair mechanisms involving neuroprogenitor cells.
Area of Science:
- Neuroscience
- Immunology
- Infectious Diseases
Background:
- Cerebral malaria (CM), a severe complication of *P. falciparum* infection, primarily affects young children.
- Neurological deficits, including seizures and developmental delays, persist in survivors of CM.
- The neuropathology underlying these long-term neurological sequelae remains poorly understood.
Purpose of the Study:
- To investigate neuronal damage in the hippocampus during experimental cerebral malaria (eCM).
- To explore the role of neuroprogenitor cells (NPCs) and potential repair mechanisms in eCM.
Main Methods:
- Utilized an experimental murine model of cerebral malaria (eCM).
- Assessed neuronal damage using NeuN and double cortin (DCX) immunostaining.
- Measured neurofilament light chain in brain tissue, CSF, and plasma.
- Examined the influx of neuroprogenitor cells into the hippocampus.
Main Results:
- *Plasmodium* infection led to extensive neuronal damage in the hippocampus, evidenced by reduced NeuN and DCX staining.
- Increased neurofilament light chain staining and CSF levels indicated neuronal fragmentation.
- An increased influx of neuroprogenitor cells was observed in eCM, suggesting repair processes.
Conclusions:
- Experimental cerebral malaria induces significant neuronal damage in the hippocampus.
- The brain shows evidence of neuronal fragmentation and an influx of neuroprogenitor cells, indicating a potential for repair.
- Further research is needed to elucidate the precise mechanisms of neuronal damage and repair in CM.
