Blood-Brain Barrier Deterioration and Hippocampal Gene Expression in Polymicrobial Sepsis: An Evaluation of Endothelial MyD88 and the Vagus Nerve

PloS One
Gerard HonigBetty Diamond

Abstract

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 ...Continue Reading

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Citations

Jun 11, 2020·Journal of Neural Engineering·Jessica D FalconeHarbaljit S Sohal
Sep 22, 2018·Frontiers in Immunology·Minakshi RanaBetty Diamond
Dec 6, 2018·Fluids and Barriers of the CNS·Jackson G DeStefanoPeter C Searson
Oct 19, 2017·Journal of Neuroscience Research·Mike Yoshio HamasakiFabiano Pinheiro da Silva
Jan 7, 2021·Endocrinology·Alice R Hill, Joanna L Spencer-Segal
Jan 29, 2021·Endocrinology·Alice R Hill, Joanna L Spencer-Segal

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Methods Mentioned

BETA
transgenic
fluorescence microscopy
biopsy
genotyping
dissection
scraping
PCR
biopsies
PCRs
Assay

Software Mentioned

ImageJ
LightCycler 480
Olympus
Primer3
LightCycler
MesoScale Workbench
UCSC Genome Browser
Primer3Plus

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