title: Early postnatal respiratory viral infection induces structural and neurochemical changes in the neonatal piglet brain.
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.
authors.affiliation: Department 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. Electronic address: mconra3@illinois.edu.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Conrad
authors.affiliation: Neuroscience Program, University of Illinois at Urbana-Champaign, Urbana, IL, USA; Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL, USA; Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
authors.forename: Bradley P
authors.initials: BP
authors.lastname: Sutton
authors.affiliation: Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Larsen
authors.affiliation: Department of Comparative Pathobiology, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: William G
authors.initials: WG
authors.lastname: Van Alstine
authors.affiliation: Department 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; Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA. Electronic address: rwjohn@illinois.edu.
authors.forename: Rodney W
authors.initials: RW
authors.lastname: Johnson
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009929:Organ Size; D019318:Porcine Reproductive and Respiratory Syndrome / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D019316:Porcine respiratory and reproductive syndrome virus; D013552:Swine
keywords: Brain; Development; Infection; Magnetic resonance imaging; Neonatal; Pig