title: The subventricular zone in the immature piglet brain: anatomy and exodus of neuroblasts into white matter after traumatic brain injury.
abstract: Stimulation of postnatal neurogenesis in the subventricular zone (SVZ) and robust migration of neuroblasts to the lesion site in response to traumatic brain injury (TBI) is well established in rodent species; however, it is not yet known whether postnatal neurogenesis plays a role in repair after TBI in gyrencephalic species. Here we describe the anatomy of the SVZ in the piglet for the first time and initiate an investigation into the effect of TBI on the SVZ architecture and the number of neuroblasts in the white matter. Among all ages of immaturity examined the SVZ contained a dense mesh network of neurogenic precursor cells (doublecortin+) positioned directly adjacent to the ependymal cells (ventricular SVZ, Vsvz) and neuroblasts organized into chains that were distinct from the Vsvz (abventricular SVZ, Asvz). Though the architecture of the SVZ was similar among ages, the areas of Vsvz and Asvz neuroblast chains declined with age. At postnatal day (PND) 14 the white matter tracts have a tremendous number of individual neuroblasts. In our scaled cortical impact model, lesion size increased with age. Similarly, the response of the SVZ to injury was also age dependent. The younger age groups that sustained the proportionately smallest lesions had the largest SVZ areas, which further increased in response to injury. In piglets that were injured at 4 months of age and had the largest lesions, the SVZ did not increase in response to injury. Similar to humans, swine have abundant gyri and gyral white matter, providing a unique platform to study neuroblasts potentially migrating from the SVZ to the lesioned cortex along these white matter tracts. In piglets injured at PND 7, TBI did not increase the total number of neuroblasts in the white matter compared to uninjured piglets, but redistribution occurred with a greater number of neuroblasts in the white matter of the hemisphere ipsilateral to the injury compared to the contralateral hemisphere. At 7 days after injury, less than 1% of neuroblasts in the white matter were born in the 2 days following injury. These data show that the SVZ in the piglet shares many anatomical similarities with the SVZ in the human infant, and that TBI had only modest effects on the SVZ and the number of neuroblasts in the white matter. Piglets at an equivalent developmental stage to human infants were equipped with the largest SVZ and a tremendous number of neuroblasts in the white matter, which may be sufficient in lesion repair without the dramatic stimulation of neurogenic machinery. It has yet to be determined whether neurogenesis and migrating neuroblasts play a role in repair after TBI and/or whether an alteration of normal migration during active postnatal population of brain regions is beneficial in species with gyrencephalic brains.
authors: Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Mass., USA.
authors: Beth A
authors: BA
authors: Costine
authors: Symeon
authors: S
authors: Missios
authors: Sabrina R
authors: SR
authors: Taylor
authors: Declan
authors: D
authors: McGuone
authors: Colin M
authors: CM
authors: Smith
authors: Carter P
authors: CP
authors: Dodge
authors: Brent T
authors: BT
authors: Harris
authors: Ann-Christine
authors: AC
authors: Duhaime
mesh_terms: D000367:Age Factors; D000818:Animals; D001930:Brain Injuries / Q000473:pathology*; D002465:Cell Movement / Q000502:physiology*; D002540:Cerebral Cortex / Q000166:cytology*; D004195:Disease Models, Animal; D005260:Female; D020547:Lateral Ventricles / Q000033:anatomy & histology* / Q000166:cytology*; D008297:Male; D058953:Neural Stem Cells / Q000166:cytology*; D055495:Neurogenesis / Q000502:physiology*; D013552:Swine; D066127:White Matter / Q000166:cytology*