University of Illinois Urbana-Champaign

Leakage of the blood-borne neuroinflammatory molecule fibrinogen correlates with microglial immunofluorescence in the fetal brain during maternal immune activation

Gonzalez-Ricon, Rafael Jaime; Otero, Ashley; Chalen, Izan; Antonson, Adrienne

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https://hdl.handle.net/2142/132823

Description

Title
Leakage of the blood-borne neuroinflammatory molecule fibrinogen correlates with microglial immunofluorescence in the fetal brain during maternal immune activation
Author(s)
  • Gonzalez-Ricon, Rafael Jaime
  • Otero, Ashley
  • Chalen, Izan
  • Antonson, Adrienne
Issue Date
2024-10-07
Keyword(s)
neurodevelopmental disorders
Date of Ingest
2026-02-22T16:57:47-06:00
Abstract
Background: Influenza A virus (IAV) infection during gestation is associated with an increased risk of neurodevelopmental disorders (NDDs) in offspring, like schizophrenia and autism spectrum disorders. The pathophysiological mechanisms underpinning this association remain a subject of investigation. We posit that maternal immune activation (MIA) precipitated by IAV infection may disrupt selective permeability at the maternal-fetal interface, consequently compromising the integrity of the fetal blood-brain barrier (BBB). This compromised barrier function could lead to aberrant trafficking of neuroinflammatory blood-borne molecules into the fetal compartment, predisposing offspring to neuroinflammatory insults implicated in NDD etiology. Our study aims to: (1) investigate whether fibrinogen, a neuroinflammatory mediator, breaches the placental and fetal brain barriers (vascular or ventricular) during MIA, and (2) determine if this correlates with microglial immunofluorescence. Methods: C57Bl/6NTac pregnant mice were inoculated with mouse-adapted IAV (103 or 104 TCID50) or saline at gestational day 9.5. Expression of tight junction proteins (TJPs) and CD31+ endothelial cells in placentas and fetal brains was assessed via qPCR and immunohistochemistry. Co-staining of fibrinogen and Iba1+ cells (microglia/macrophages) was assessed in the subventricular zone (SVZ) of the lateral ventricle in fetal brains. Results: No statistical differences were seen regarding TJPs and CD31+ quantification in placentas or fetal brains. A significant increase in fibrinogen levels was noted in fetal brains exposed to 104 TCID50 IAV versus other groups. Moreover, a positive correlation between fibrinogen and Iba1+ staining at the SVZ was noted. Conclusion: Large neuroinflammatory glycoprotein fibrinogen can reach the fetal brain during IAV infection. We detected increased correlation in fibrinogen leakage and Iba1+ cell immunofluorescence mainly at the SVZ. Ongoing experiments will determine potential origin and trafficking of other blood-borne molecules that might be implicated in fetal neuroinflammation upon MIA.
Publisher
Society for Neuroscience
Series/Report Name or Number
Neuroscience 2024
Type of Resource
text
Genre of Resource
conference paper

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