Drobyshevsky Alexander, Quinlan Katharina A
Department of Pediatric, NorthShore University HealthSystem Research Institute, Evanston, IL, United States.
Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States.
Exp Neurol. 2017 Jul;293:13-26. doi: 10.1016/j.expneurol.2017.03.017. Epub 2017 Mar 24.
While antenatal hypoxia-ischemia (H-I) is a well-established cause of brain injury, the effects of H-I on the spinal cord remain undefined. This study examined whether hypertonia in rabbits was accompanied by changes in spinal architecture. Rabbit dams underwent global fetal H-I at embryonic day 25 for 40min. High resolution diffusion tensor imaging was performed on fixed neonatal CNS. Fractional anisotropy (FA) and regional volumetric measurements were compared between kits with and without hypertonia after H-I and sham controls using Tract Based Spatial Statistics. Hypertonic kits showed evidence of damage from hypoxia not only in the brain, but in spinal cord as well. Hypertonic kits showed reduced FA and thickness in corticospinal tracts, external capsule, fimbria, and in white and gray matter of both cervical and lumbar spinal cord. Dorsal white matter of the spinal cord was the exception, where there was thickening and increased FA in hypertonic kits. Direct damage to the spinal cord was demonstrated in a subset of dams imaged during H-I with a 3T magnetic resonance scanner, where apparent diffusion coefficient in fetal spinal cords acutely decreased during hypoxia. Hypertonic kits showed subsequent decreases in lumbar motoneuron counts and extensive TUNEL- and Fluoro-Jade C-positive labeling was present in the spinal cord 48h after H-I, demonstrating spinal neurodegeneration. We speculate that global H-I causes significant loss of both spinal white and gray matter in hypertonic newborns due to direct H-I injury to the spinal cord as well as due to upstream brain injury and consequent loss of descending projections.
虽然产前缺氧缺血（H-I）是脑损伤的一个公认原因，但H-I对脊髓的影响仍不明确。本研究检测了兔的张力亢进是否伴有脊髓结构的改变。孕兔在胚胎第25天经历40分钟的全胎儿H-I。对固定的新生中枢神经系统进行高分辨率扩散张量成像。使用基于纤维束的空间统计学方法，比较了H-I后有和没有张力亢进的幼崽以及假手术对照组之间的分数各向异性（FA）和区域体积测量值。张力亢进的幼崽不仅在脑内，而且在脊髓中也显示出缺氧损伤的证据。张力亢进的幼崽在皮质脊髓束、外囊、伞以及颈段和腰段脊髓的白质和灰质中显示FA降低和厚度减小。脊髓背侧白质是个例外，张力亢进的幼崽中此处有增厚和FA增加。在H-I期间用3T磁共振扫描仪成像的一部分母兔中证实了脊髓的直接损伤，其中胎儿脊髓的表观扩散系数在缺氧期间急剧下降。张力亢进的幼崽随后腰段运动神经元数量减少，并且在H-I后48小时脊髓中存在广泛的TUNEL和氟玉髓C阳性标记，表明脊髓神经变性。我们推测，全脑H-I会导致张力亢进的新生儿脊髓白质和灰质大量丢失，这是由于脊髓受到直接的H-I损伤以及上游脑损伤和随之而来的下行投射丧失所致。
