Blood-cerebrospinal fluid barrier: another site disrupted during experimental cerebral malaria caused by Plasmodium berghei ANKA

概要

Cerebral malaria (CM) is one of the most severe pathologies of malaria; it induces neu ro-cognitive sequela and has a high mortality rate. Although many factors involved in the development of CM have been discovered, its pathogenic mechanisms are still no t completely understood. Most studies on CM have focused on the blood–brain barrie r (BBB), despite the importance of the blood–cerebrospinal fluid barrier (BCSFB), whi ch protects the brain from peripheral inflammation. Consequently, the pathological r ole of the BCSFB in CM is currently unknown. To examine the status of the BCSFB i n CM and malaria without this pathology (non-CM), we developed a new method for e valuating the permeabilization of the BCSFB during CM in mice, using Evans blue dy e and a software-assisted image analysis. Using C57BL/6J (B6) mice infected with Pl asmodium berghei ANKA as an experimental CM model and B6 mice infected with P. berghei NK65 or Plasmodium yoelii as non-CM models, we revealed that the permeabi lity of the BCSFB increased during experimental CM but not during non-CM. We obs erved hemorrhaging in the cerebral ventricles and hemozoin-like structures in the ch oroid plexus, which is a key component of the BCSFB, in CM mice. Taken together, t his evidence indicates that the BCSFB is disrupted in experimental CM, whereas it re mains intact in non-CM. We also found that P. berghei ANKA parasites and CD8+ T ce lls are involved in the BCSFB disruption in experimental CM. An understanding of th e mechanisms underlying CM might help in the development of effective strategies to prevent and manage CM in humans.