Role of the blood-brain barrier and blood-CSF barrier in the pathogenesis of bacterial meningitis

Abstract

Despite significant progress in prevention, diagnosis and therapy acute bacterial menin- gitis remains an important cause of high morbidity and mortality in the pediatric popula- tion with no significant improvement in the outcome in recent years. Further ameliora- tion in treatment can only result from a better understanding of the pathophysiological events that occur after activation of the host’s inflammatory pathways secondary to initial bacterial invasion. The need for improved management strategies is highlighted by the observed increase in antibiotic resistance of microbial pathogens and recent develop- ments in the pharmacological treatment of meningitis patients with dexamethasone, which might adversely influence delivery of drugs to the central nervous system (CNS). In this respect the cellular and molecular events at the blood-CNS barriers come to the focus of attention. It has become evident that these anatomical and functional barriers with their differentiated functionality and vast surface area centrally contribute to the development of bacterial meningitis. This holds true not only for their role as a port of entry into the CNS but also as key players in the pathophysiological cascade following bacterial invasion into the brain. Important aspects that have to be considered are the unique anatomical and functional features of the blood-brain barrier and the blood- cerebrospinal fluid barrier, and their distinct interactions with the variety of pathogens responsible for the development of bacterial meningitis.