Data from: Blood-brain barrier deterioration and hippocampal gene expression in polymicrobial sepsis: an evaluation of endothelial MyD88 and the vagus nerve

Systemic infection can initiate or exacerbate central nervous system (CNS)
pathology, even in the absence of overt invasion of bacteria into the CNS.
Recent epidemiological studies have demonstrated that human survivors of
sepsis have an increased risk of long-term neurocognitive decline. There
is thus a need for improved understanding of the physiological mechanisms
whereby acute sepsis affects the CNS. In particular, MyD88-dependent
activation of brain microvascular endothelial cells and a resulting loss
of blood-brain barrier integrity have been proposed to play an important
role in the effects of systemic inflammation on the CNS. Signaling through
the vagus nerve has also been considered to be an important component of
CNS responses to systemic infection. Here, we demonstrate that blood-brain
barrier permeabilization and hippocampal transcriptional responses during
polymicrobial sepsis occur even in the absence of MyD88-dependent
signaling in cerebrovascular endothelial cells. We further demonstrate
that these transcriptional responses can occur without vagus nerve input.
These results suggest that redundant signals mediate CNS responses in
sepsis. Either endothelial or vagus nerve activation may be individually
sufficient to transmit systemic inflammation to the central nervous
system. Transcriptional activation in the forebrain in sepsis may be
mediated by MyD88-independent endothelial mechanisms or by non-vagal
neuronal pathways.