Department of Neonatology, Children's Hospital of Fudan University, Shanghai, China.
Brain Res. 2009 Dec 8;1301:100-9. doi: 10.1016/j.brainres.2009.09.006. Epub 2009 Sep 10.
Although periventricular white matter injury is a leading cause of major neurologic disability in premature infants, the relationship between myelination deficiency and long-term cognitive dysfunction is not well understood. The purpose of this study was to investigate oligodendrocytes myelination and long-term spatial cognitive function in rats with perinatal hypoxia-ischemia (HI). Postnatal day 3 (P3) rats were subjected to right carotid artery ligation followed by 2.5 h of hypoxia (6% oxygen). Brain injury during the early and late phases was evaluated by immunostaining at P6 (72 h after the injury) and P47. Spatial cognitive function was evaluated at P42 using the Morris Water Maze test followed by histologic evaluation. HI caused an increase in pre-oligodendrocytes, astrocytes, and microglia in the ipsilateral white matter 72 h after the insult compared to contralateral regions and sham-operated controls (both p<0.05). There were significant decreases in myelin basic protein (MBP)and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase)-labeled oligodendrocytes with glial fibrillary acidic protein (GFAP)-labeled glial scarring in the ipsilateral periventricular white matter at P47 compared to contralateral regions and sham-operated controls (all p<0.05). The rats with HI had spatial learning deficits in navigation trials (longer escape latency and swimming distance) and memory dysfunction in probe trials (fewer number of platform crossings and percentage of time in the target quadrant) compared with sham-operated controls (p<0.05). In this neonatal rat model of HI, myelination deficiency induced by activated astrocytes and microglia during the early phase with subsequent glial scarring was associated with long-term spatial learning and memory dysfunction.
尽管脑室周围白质损伤是早产儿主要神经功能障碍的主要原因，但髓鞘形成不足与长期认知功能障碍之间的关系尚不清楚。本研究旨在研究围产期缺氧缺血（HI）大鼠少突胶质细胞髓鞘形成和长期空间认知功能。在产后第 3 天（P3），大鼠进行右侧颈总动脉结扎，随后进行 2.5 小时缺氧（6%氧气）。在 P6（损伤后 72 小时）和 P47 时通过免疫染色评估早期和晚期脑损伤。在 P42 时使用 Morris 水迷宫测试评估空间认知功能，然后进行组织学评估。与对侧区域和假手术对照组相比，HI 导致同侧白质中前少突胶质细胞、星形胶质细胞和小胶质细胞在损伤后 72 小时增加（均 p<0.05）。与对侧区域和假手术对照组相比，在 P47 时同侧脑室周围白质中髓鞘碱性蛋白（MBP）和 2'，3'-环核苷酸 3'-磷酸二酯酶（CNPase）标记的少突胶质细胞减少，而胶质纤维酸性蛋白（GFAP）标记的神经胶质瘢痕形成（均 p<0.05）。与假手术对照组相比，HI 大鼠在导航试验中存在空间学习缺陷（潜伏期和游泳距离较长），在探针试验中存在记忆功能障碍（平台穿越次数减少和目标象限时间百分比减少）（均 p<0.05）。在这种新生大鼠 HI 模型中，早期激活的星形胶质细胞和小胶质细胞诱导的髓鞘形成不足，随后发生神经胶质瘢痕形成，与长期空间学习和记忆功能障碍有关。
