Blood-brain barrier function in cerebral malaria and CNS infections in Vietnam

Background: The intraerythrocytic parasite Plasmodium falciparum induces th e life-threatening neurologic syndrome of cerebral malaria (CM) from within cerebral blood vessels, without entering the brain parenchyma. Objectives: 1) To assess the use of CSF as an indicator of specific pathologic process es occurring in the brain during CM; 2) to compare this with other neurolog ic and infectious diseases to understand the distinct pathogenic features o f CM; 3) to test the hypothesis that CM involves a specific functional brea kdown of the blood-brain barrier (BBB). Methods: 1) Radial immunodiffusion assays to detect albumin and IgG in matched plasma and CSF samples as indic ators of BBB integrity and intrathecal IgG production; and 2) ELISA for sol uble intracellular adhesion molecule-1 and sE-selectin, the cytokines tumor necrosis factor-alpha and transforming growth factor-beta 1, and the matri x metalloproteinase MMP-9, to detect cellular activation and inflammatory r esponses within the brain. Results: Albumin and IgG indices implied only mi nimal degree of BBB breakdown in a few cases of CM, with most remaining wit hin the normal range. In contrast, cryptococcal, tubercular, and acute bact erial meningitis produced detectable changes in the composition of the CSF and evidence of BBB breakdown. Conclusions: CM appears to involve only subt le functional changes in BBB integrity with minimal intraparenchymal inflam matory responses compared with other neurologic infections. This focuses at tention on local events within and around the cerebral microvasculature in CM, rather than indicating widespread parenchymal disease.