Middle ear
infection (or
inflammation) is the most common pathological condition that causes fluid to accumulate in the middle ear, disrupting cochlear homeostasis.
Lipopolysaccharide, a product of bacteriolysis, activates macrophages and causes release of inflammatory
cytokines. Many studies have shown that
lipopolysaccharides cause functional and structural changes in the inner ear similar to that of
inflammation. However, it is specifically not known how
lipopolysaccharides affect the blood-labyrinth barrier in the stria vascularis (intra-strial fluid-blood barrier), nor what the underlying mechanisms are. In this study, we used a cell culture-based in vitro model and animal-based in vivo model, combined with immunohistochemistry and a vascular leakage assay, to investigate
lipopolysaccharide effects on the integrity of the mouse intra-strial fluid-blood barrier. Our results show
lipopolysaccharide-induced local
infection significantly affects intra-strial fluid-blood barrier component cells. Pericytes and perivascular-resident macrophage-like melanocytes are particularly affected, and the morphological and functional changes in these cells are accompanied by substantial changes in barrier integrity. Significant vascular leakage is found in the
lipopolysaccharide treated-animals. Consistent with the findings from the in vivo animal model, the permeability of the endothelial cell monolayer to
FITC-albumin was significantly higher in the
lipopolysaccharide-treated monolayer than in an untreated endothelial cell monolayer. Further study has shown the
lipopolysaccharide-induced
inflammation to have a major effect on the expression of tight junctions in the blood barrier.
Lipopolysaccharide was also shown to cause
high frequency hearing loss, corroborated by previous reports from other laboratories. Our findings show
lipopolysaccharide-evoked middle ear
infection disrupts inner ear fluid balance, and its particular effects on the intra-strial fluid-blood barrier, essential for cochlear homeostasis. The barrier is degraded as the expression of tight junction-associated
proteins such as
zona occludens 1,
occludin, and
vascular endothelial cadherin are down-regulated.