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.

The Effects of a Glucocorticoid Receptor Agonist (GRA) on the Immune Function, Nutrient Digestibility, and Wean-to-Finish Growth Performance of Early-Weaned Pigs

“…As a result, a severe reduction in growth during the first seven to ten days post-weaning is observed [ 2 , 19 , 20 ]. While detrimental during the weaning period, evidence suggests that the physiological effects of weaning also lead to lifelong impairments in gut health, as well as sensitivity to stress and immune challenges [ 8 , 9 , 21 , 22 ]. Moreover, the period of growth immediately following weaning directly impacts how fast pigs reach market weight [ 5 , 6 ].…”

“…This period of growth is of particular importance because it can negatively affect the lifelong productivity of pigs [ 5 , 6 , 7 ]. Furthermore, evidence suggests that inflammation and gut dysfunction during early weaning results in lifelong hyper-reactivity to stress and immune challenges [ 8 , 9 ]. Recently, antibiotics have been fed during early weaning to promote gut health and reduce inflammation [ 10 , 11 ].…”

Postnatal Iron Deficiency Alters Brain Development in Piglets

“…previously described by Radlowski et al (19) and Conrad et al (15,20). Clusters consisting of <20 edge-connected clusters were not considered for analysis.…”