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demonstrate that adjunctive treatment with dexamethasone was detrimental in
hippocampal apoptosis, while hypertonic saline was beneficial (
Spreer et al.,
2006
;
Liu et al., 2011
). Recent studies suggest an endogenous potential of neural
progenitor cell renewal in the hippocampal formation in bacterial meningitis
(
Gerber et al., 2009
;
Hofer et al., 2011
) and studies are needed to determine
whether stimulation of endogenous neurogenesis can be used as a potential
option in survivors of bacterial meningitis.
CONCLUSIONS
A major limitation to advances in prevention and therapy of
E. coli
meningitis
is our incomplete understanding of the pathogenesis and pathophysiology of
this disease. Given the plethora of
E. coli
serotypes, it is unclear why K1 and
limited numbers of O types of
E. coli
phylogenetic groups B2 and D account
for most cases of meningitis. As indicated above, studies with the in vitro and
in vivo blood-brain barrier models have shed light on the mechanisms of micro-
bial translocation of the blood-brain barrier, a key step for the development of
meningitis. We have shown that
E. coli
traverses the blood-brain barrier without
altering the integrity of the HBMEC monolayer and without affecting blood-
brain barrier permeability as well as without accompanying infiltrating phago-
cytes (
Kim et al., 1992, 1997
;
Stins et al., 2001
).
E. coli
K1 penetration into
the brain requires a high degree of bacteremia, and
E. coli
binding to and inva-
sion of HBMEC, as well as traversal of the blood-brain barrier as live bacteria.
E. coli
invasion of the blood-brain barrier occurs as the result of specific bacte-
ria-host interactions involving specific host cell signal transduction pathways.
Complete understanding of the microbial-host factors that are involved in
E. coli
penetration of the blood-brain barrier as well as
E. coli
-induced neuronal
injury should help in developing new strategies for prevention and therapy of
E. coli
meningitis and associated neuronal injury.
ACKNOWLEDGMENTS
This work was supported by NIH grants R01 NS 26310 and AI 84984.
REFERENCES
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