E. coli Invasion of Brain Microvascular Endothelial Cells as a Pathogenetic Basis of Meningitis
Bacterial meningitis still results in a high mortality and morbidity despite advances in antimicrobial chemotheraphy and supportive care (Durand et al., 1993; Unhanand et al., 1993). Both clinical and experimental data indicate limited efficacy with antimicrobial chemotherapy alone (Kim, 1985; McCracken et al., 1984). A major contributing factor is the incomplete understanding of the pathogenesis and pathophysiology associated with the bacterial meningitis. For example, most cases of bacterial meningitis develop as a result of hematogenous spread, but it is not clear how circulating bacteria cross the blood-brain barrier. We have utilized E.coli as a paradigm to examine how circulating bacteria traverse the blood-brain barrier. In addition, E. coli is the most common gram-negative bacterium that causes meningitis, particularly during the neonatal period. Our investigations have become feasible with the availability of both in vitro and in vivo models of the blood-brain barrier.
KeywordsMeningitis Tetracycline Dextran Gentamicin Colchicine
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