title: A neonatal piglet model for investigating brain and cognitive development in small for gestational age human infants.
abstract: The piglet was investigated as a potential model for studying brain and cognitive deficits associated with being born small for gestational age (SGA). Naturally farrowed SGA (0.7-1.0 kg BW) and average for gestational age (AGA, 1.3-1.6 kg BW) piglets were obtained on postnatal day (PD) 2, placed in individual cages, and provided a nutritionally adequate milk replacer diet (285 ml/kg/d). Beginning at PD14, performance in a spatial T-maze task was assessed. At PD28, piglets were anesthetized for magnetic resonance (MR) imaging to assess brain structure (voxel-based morphometry), connectivity (diffusion-tensor imaging) and metabolites in the hippocampus and corpus callosum (proton MR spectroscopy). Piglets born SGA showed compensatory growth such that BW of SGA and AGA piglets was similar (P>0.05), by PD15. Birth weight affected maze performance, with SGA piglets taking longer to reach criterion than AGA piglets (p<0.01). Total brain volume of SGA and AGA piglets was similar (P<0.05), but overall, SGA piglets had less gray matter than AGA piglets (p<0.01) and tended to have a smaller internal capsule (p = 0.07). Group comparisons between SGA and AGA piglets defined 9 areas (≥ 20 clusters) where SGA piglets had less white matter (p<0.01); 2 areas where SGA piglets had more white matter (p<0.01); and 3 areas where SGA piglets had more gray matter (p<0.01). The impact of being born SGA on white matter was supported by a lower (p<0.04) fractional anisotropy value for SGA piglets, suggesting reduced white matter development and connectivity. None of the metabolites measured were different between groups. Collectively, the results show that SGA piglets have spatial learning deficits and abnormal development of white matter. As learning deficits and abnormalities in white matter are common in SGA human infants, the piglet is a tractable translational model that can be used to investigate SGA-associated cognitive deficits and potential interventions.
authors.affiliation: Department of Animal Sciences, University of Illinois, Urbana, Illinois, United States of America; Division of Nutritional Sciences, University of Illinois, Urbana, Illinois, United States of America.
authors.forename: Emily C
authors.initials: EC
authors.lastname: Radlowski
authors.affiliation: Neuroscience Program, University of Illinois, Urbana, Illinois, United States of America.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Conrad
authors.affiliation: Department of Veterinary Pathobiology, University of Illinois, Urbana, Illinois, United States of America.
authors.forename: Stephane
authors.initials: S
authors.lastname: Lezmi
authors.affiliation: Department of Animal Sciences, University of Illinois, Urbana, Illinois, United States of America; Division of Nutritional Sciences, University of Illinois, Urbana, Illinois, United States of America; Neuroscience Program, University of Illinois, Urbana, Illinois, United States of America.
authors.forename: Ryan N
authors.initials: RN
authors.lastname: Dilger
authors.affiliation: Neuroscience Program, University of Illinois, Urbana, Illinois, United States of America; Department of Bioengineering, University of Illinois, Urbana, Illinois, United States of America.
authors.forename: Brad
authors.initials: B
authors.lastname: Sutton
authors.affiliation: Biomedical Imaging Center, Beckman Institute, University of Illinois, Urbana, Illinois, United States of America.
authors.forename: Ryan
authors.initials: R
authors.lastname: Larsen
authors.affiliation: Department of Animal Sciences, University of Illinois, Urbana, Illinois, United States of America; Division of Nutritional Sciences, University of Illinois, Urbana, Illinois, United States of America; Neuroscience Program, University of Illinois, Urbana, Illinois, United States of America.
authors.forename: Rodney W
authors.initials: RW
authors.lastname: Johnson
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight; D001921:Brain / Q000033:anatomy & histology / Q000254:growth & development / Q000502:physiology*; D002657:Child Development; D003071:Cognition / Q000502:physiology*; D056324:Diffusion Tensor Imaging; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age / Q000254:growth & development*; D009682:Magnetic Resonance Spectroscopy; D018782:Maze Learning; D023421:Models, Animal; D009929:Organ Size; D013552:Swine