Costine Beth A, Missios Symeon, Taylor Sabrina R, McGuone Declan, Smith Colin M, Dodge Carter P, Harris Brent T, Duhaime Ann-Christine
Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Mass., USA.
Dev Neurosci. 2015;37(2):115-30. doi: 10.1159/000369091. Epub 2015 Feb 10.
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.
在啮齿类动物中，室管膜下区（SVZ）的产后神经发生受到刺激以及神经母细胞对创伤性脑损伤（TBI）作出反应并向损伤部位进行强劲迁移已得到充分证实；然而，在脑回物种中，产后神经发生是否在TBI后的修复过程中发挥作用尚不清楚。在此，我们首次描述了仔猪SVZ的解剖结构，并开始研究TBI对SVZ结构以及白质中神经母细胞数量的影响。在所有检查的未成熟年龄段中，SVZ包含一个密集的神经源性前体细胞（双皮质素阳性）网状网络，这些细胞直接毗邻室管膜细胞（室周SVZ，Vsvz），神经母细胞则组织成链，与Vsvz不同（室管膜下SVZ，Asvz）。尽管SVZ的结构在各年龄段相似，但Vsvz和Asvz神经母细胞链的面积随年龄增长而减小。在出生后第14天（PND 14），白质束中有大量单个神经母细胞。在我们的标准化皮质撞击模型中，损伤大小随年龄增加。同样，SVZ对损伤的反应也依赖于年龄。遭受相对最小损伤的较年轻年龄组具有最大的SVZ面积，损伤后该面积进一步增加。在4月龄时受伤且损伤最大的仔猪中，SVZ对损伤没有反应。与人类相似，猪有丰富的脑回和脑回白质，为研究神经母细胞可能沿着这些白质束从SVZ迁移到损伤皮质提供了一个独特的平台。在PND 7时受伤的仔猪中，与未受伤仔猪相比，TBI并未增加白质中神经母细胞的总数，但发生了重新分布，与对侧半球相比，损伤同侧半球白质中的神经母细胞数量更多。在损伤后7天，白质中不到1%的神经母细胞是在损伤后2天内产生的。这些数据表明，仔猪的SVZ与人类婴儿的SVZ在许多解剖学上具有相似性，并且TBI对SVZ和白质中神经母细胞数量的影响较小。处于与人类婴儿相当发育阶段的仔猪具有最大的SVZ和白质中大量的神经母细胞，这在损伤修复中可能足够，而无需神经发生机制的剧烈刺激。神经发生和迁移的神经母细胞是否在TBI后的修复中发挥作用，以及/或者在脑区活跃的产后细胞增殖过程中正常迁移的改变在脑回脑物种中是否有益，还有待确定。
