Minocycline inhibits microglial activation in the CA1 hippocampal region and prevents long-term cognitive sequel after experimental cerebral malaria.

Cerebral malaria is the worst complication of malaria infection, has a high mortality rate, and may cause different neurodysfunctions, including cognitive decline. Neuroinflammation is an important cause of cognitive damage in neurodegenerative diseases, and microglial cells can be activated in a disease-associated profile leading to tissue damage and neuronal death. Here, we demonstrated that treatment with minocycline reduced blood-brain barrier breakdown and modulated ICAM1 mRNA expression; reduced proinflammatory cytokines, such as TNF-α, IL-1β, IFN-γ, and IL-6; and prevented long-term cognitive decline in contextual and aversive memory tasks. Taken together, our data suggest that microglial cells are activated during experimental cerebral malaria, leading to neuroinflammatory events that end up in cognitive damage. In addition, pharmacological modulation of microglial activation, by drugs such as minocycline may be an important therapeutic strategy in the prevention of long-term memory impairment.