University of Illinois Urbana-Champaign

Fibrinogen Accumulation, Oxidative Stress, and Apoptosis in the Fetal Brain Induced by Maternal Influenza A Virus Infection

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

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https://hdl.handle.net/2142/132820

Description

Title
Fibrinogen Accumulation, Oxidative Stress, and Apoptosis in the Fetal Brain Induced by Maternal Influenza A Virus Infection
Author(s)
  • Gonzalez-Ricon, Rafael Jaime
  • Otero, Ashley
  • Antonson, Adrianne M
  • Chalen, Izan
Issue Date
2025-11-19
Keyword(s)
  • Influenza
  • neurodevelopmental disorders
Date of Ingest
2026-02-22T16:46:02-06:00
Abstract
Maternal influenza A virus (IAV) infection during pregnancy is a risk factor for neurodevelopmental disorders (NDDs) in offspring. Oxidative stress, triggered by an imbalance between reactive oxygen species (ROS) and antioxidant defenses, is a key mechanism in NDD pathogenesis. Fibrinogen, a plasma protein known for its role in coagulation, has also been associated with neurodegenerative inflammation and oxidative responses after breaching the blood-brain barrier. However, its presence and potential contribution to oxidative stress and apoptosis in the fetal brain following IAV-induced maternal immune activation (MIA) is unknown. We hypothesize that compromised vascular integrity following maternal IAV infection contributes to microglial response and subsequent neuronal loss in the developing fetal brain. Pregnant C57BL/6NTac mice were intranasally inoculated with IAV (10⁴ TCID₅₀) or saline at gestational day (GD) 9.5. Fetal brains were collected at GD16.5 to assess apoptosis in Sox2⁺ and NeuN⁺ cells via cleaved caspase-3 and DNA fragmentation (ApopTag Red). To examine microglial ROS production and potential stimulation by fibrinogen, phosphorylated p47phox—a cytosolic subunit of NADPH oxidase—will be measured in P2RY12⁺ microglia alongside fibrinogen labeling. Our findings show increased fibrinogen accumulation in neurogenic regions of fetal brains exposed to maternal IAV, which positively correlates with Iba1 immunofluorescence. Preliminary data indicate region-specific apoptosis in subventricular zones and elevated ROS production in the meninges and cortex. Ongoing experiments will determine whether this region specificity contributes to long term disruptions in neuronal differentiation and circuit wiring. These results suggest that maternal IAV infection increases fetal blood-brain barrier permeability, as evidenced by fibrinogen accumulation in neurogenic regions. This extravasation of fibrinogen may stimulate microglial/macrophage oxidative responses and contribute to apoptotic cell death, highlighting a potential mechanistic link between MIA, blood-brain barrier dysfunction, and disrupted fetal brain development.
Publisher
Society for Neuroscience
Series/Report Name or Number
Neuroscience 2025
Type of Resource
text
Genre of Resource
conference paper

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