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Use of a Piglet Model for the Study of Anesthetic-induced Developmental Neurotoxicity AIDN: A Translational Neuroscience Approach
Published on: June 11, 2017
Early postnatal respiratory viral infection induces structural and neurochemical changes in the neonatal piglet brain
Matthew S Conrad1, Bradley P Sutton2, Ryan Larsen3
1Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA; Neuroscience Program, University of Illinois at Urbana-Champaign, Urbana, IL, USA; Integrative Immunology and Behavior Program, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
Insights
Early-life infections like porcine reproductive and respiratory syndrome virus (PRRSV) can significantly impact brain development in infant mammals. This study shows PRRSV infection alters brain structure and neurochemistry in piglets, highlighting risks for brain growth.
Area of Science:
- Neuroscience
- Developmental Biology
- Infectious Disease
Background:
- Postnatal infections causing inflammation are common but their effects on brain development in gyrencephalic species are poorly understood.
- Domestic piglets share similar brain growth and morphology with human infants, making them a relevant model for studying early-life infection impacts.
Purpose of the Study:
- To investigate the impact of porcine reproductive and respiratory syndrome virus (PRRSV) infection on brain development in piglets.
- To assess changes in brain macrostructure, microstructure, and neurochemistry following experimental PRRSV-induced pneumonia.
Main Methods:
- Domestic piglets were inoculated with PRRSV on postnatal day 7.
- Magnetic resonance imaging (MRI), including voxel-based morphometry, diffusion tensor imaging, and MR-spectroscopy, was used to analyze brain changes at postnatal day 29 or 30.
- Plasma TNFα levels were measured to assess the systemic inflammatory response.
Main Results:
- PRRSV infection led to increased ventricular system volumes and altered gray and white matter volumes in specific brain regions, including the primary visual cortex.
- Reduced fractional anisotropy was observed in the corpus callosum of PRRSV-infected piglets.
- Decreased levels of N-acetylaspartate, creatine, and myo-inositol in the hippocampus suggested disrupted neuronal and glial health and energy imbalances.
Conclusions:
- Early-life PRRSV infection significantly affects brain growth and development in a gyrencephalic species.
- Findings demonstrate that postnatal inflammation can lead to structural and neurochemical alterations in the developing brain.
- This model provides insights into the potential neurological consequences of early-life infections in species with complex brain development.
Abstract:
Infections that cause inflammation during the postnatal period are common, yet little is known about their impact on brain development in gyrencephalic species. To address this issue, we investigated brain development in domestic piglets which have brain growth and morphology similar to human infants, after experimentally infecting them with porcine reproductive and respiratory syndrome virus (PRRSV) to induce an interstitial pneumonia Piglets were inoculated with PRRSV on postnatal day (PD) 7 and magnetic resonance imaging (MRI) was used to assess brain macrostructure (voxel-based morphometry), microstructure (diffusion tensor imaging) and neurochemistry (MR-spectroscopy) at PD 29 or 30. PRRSV piglets exhibited signs of infection throughout the post-inoculation period and had elevated plasma levels of TNFα at the end of the study. PRRSV infection increased the volume of several components of the ventricular system including the cerebral aqueduct, fourth ventricle, and the lateral ventricles. Group comparisons between control and PRRSV piglets defined 8 areas where PRRSV piglets had less gray matter volume; 5 areas where PRRSV piglets had less white matter volume; and 4 relatively small areas where PRRSV piglets had more white matter. Of particular interest was a bilateral reduction in gray and white matter in the primary visual cortex. PRRSV piglets tended to have reduced fractional anisotropy in the corpus callosum. Additionally, N-acetylaspartate, creatine, and myo-inositol were decreased in the hippocampus of PRRSV piglets suggesting disrupted neuronal and glial health and energy imbalances. These findings show in a gyrencephalic species that early-life infection can affect brain growth and development.

