Lethal versus surviving sepsis phenotypes displayed a partly differential regional expression of neurotransmitters and inflammation and did not modify the blood-brain barrier permeability in female CLP mice

Fatemeh Azizian-Farsani; Katrin Weixelbaumer; Daniel Mascher; Andrea Klang; Sandra Högler; Nora Dinhopl; Barbara Bauder; Herbert Weissenböck; Alexander Tichy; Peter Schmidt; Marcin F. Osuchowski; Hermann Mascher

doi:10.1186/s40635-024-00688-7

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Title (eng)

Lethal versus surviving sepsis phenotypes displayed a partly differential regional expression of neurotransmitters and inflammation and did not modify the blood-brain barrier permeability in female CLP mice

Author

Fatemeh Azizian-Farsani

Katrin Weixelbaumer

Daniel Mascher

Andrea Klang

Sandra Högler

Nora Dinhopl

Barbara Bauder

Herbert Weissenböck

Alexander Tichy

Peter Schmidt

Marcin F. Osuchowski

Hermann Mascher

Abstract (eng)

Septic encephalopathy is frequent but its pathophysiology is enigmatic. We studied expression of neurotransmitters, inflammation and integrity of the blood-brain barrier (BBB) in several brain regions during abdominal sepsis. We compared mice with either lethal or surviving phenotype in the first 4 sepsis days. Mature CD-1 females underwent cecal ligation and puncture (CLP). Body temperature (BT) was measured daily and predicted-to-die (within 24 h) mice (for P-DIE; BT??35 °C), and healthy controls (CON). Brains were dissected into neocortex, cerebellum, midbrain, medulla, striatum, hypothalamus and hippocampus.CLP mice showed an up to threefold rise of serotonin in the hippocampus, 5-hydroxyindoleacetic and homovanillic acid (HVA) in nearly all regions vs. CON. Compared to P-SUR, P-DIE mice showed a 1.7 to twofold rise of HVA (386 ng/g of tissue), dopamine (265 ng/g) and 3,4-Dihydroxyphenylacetic acid (DOPAC; 140 ng/g) in the hippocampus, hypothalamus and medulla (174, 156, 82 ng/g of tissue, respectively). CLP increased expression of TNF?, IL-1? and IL-6 mRNA by several folds in the midbrain, cerebellum and hippocampus versus CON. The same cytokines were further elevated in P-DIE vs P-SUR in the midbrain and cerebellum. Activation of astrocytes and microglia was robust across regions but remained typically phenotype independent. There was a similar influx of sodium fluorescein across the BBB in both P-DIE and P-SUR mice.Compared to survivors, the lethal phenotype induced a stronger deregulation of amine metabolism and cytokine expression in selected brain regions, but the BBB permeability remained similar regardless of the predicted outcome.

Keywords (eng)

Septic EncephalopathyCognitive ImpairmentAmino-AcidMicrogliaModelsDeliriumShockratMetabolismExposure

Type (eng)

journal article

Language

[eng]

Persistent identifier

https://phaidra.vetmeduni.ac.at/o:3800

DOI

10.1186/s40635-024-00688-7

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Title (eng)