Jansen E M, Solberg L, Underhill S, Wilson S, Cozzari C, Hartman B K, Faris P L, Low W C
Department of Neurosurgery, Graduate Program in Neuroscience, University of Minnesota Medical School, Minneapolis 55455, USA.
Exp Neurol. 1997 Oct;147(2):487-97. doi: 10.1006/exnr.1997.6596.
Ischemic brain injury in neonates can result in the degeneration of cortical and subcortical areas of brain and is associated with neurologic deficits. One approach to restoring function in conditions of ischemic brain injury is the use of neural transplants to repair damaged connections. This approach has been shown to reestablish neural circuitry and to ameliorate associated motor deficits in models of neonatal sensorimotor cortex damage. In this study, we utilized the Rice et al. rodent model of neonatal ischemic-hypoxic (IH) brain injury to assess whether transplantation of fetal neocortical tissue can promote functional recovery in tests of sensorimotor and locomotor ability throughout development and as adults. We show that animals that received neocortical grafts 3 days following the IH injury performed significantly better as adults on two measures of motor ability, the Rota-Rod treadmill and apomorphine-induced rotations, than did control animals that received sham transplants after the IH injury. Transplants were identifiable in 72% of the animals 10-12 weeks after implantation. Histochemical studies revealed that while the transplanted tissue did not establish normal cortical cytoarchitecture, cells and fibers within the grafts stained for nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d), choline acetyl transferase (ChAT), cholecystokinin (CCK), and glial fibrillary acidic protein (GFAP). These results suggest that transplantation of fetal neocortical tissue following IH injury in the neonatal period is associated with amelioration of motor deficits and that the grafted tissue demonstrated a neurochemical phenotype that resembled normal neocortex. This approach warrants continued investigation in light of potential therapeutic uses.
新生儿缺血性脑损伤可导致大脑皮质和皮质下区域退化，并伴有神经功能缺损。在缺血性脑损伤情况下恢复功能的一种方法是使用神经移植来修复受损连接。在新生儿感觉运动皮质损伤模型中，这种方法已被证明可重建神经回路并改善相关的运动功能缺损。在本研究中，我们利用赖斯等人的新生鼠缺血缺氧（IH）脑损伤模型，评估胎儿新皮质组织移植是否能在整个发育过程及成年后促进感觉运动和运动能力测试中的功能恢复。我们发现，在IH损伤后3天接受新皮质移植的成年动物，在两项运动能力测试（转棒跑步机测试和阿扑吗啡诱导旋转测试）中的表现明显优于在IH损伤后接受假移植的对照动物。移植后10 - 12周，72%的动物体内可识别出移植组织。组织化学研究表明，虽然移植组织未形成正常的皮质细胞结构，但移植组织内的细胞和纤维对烟酰胺腺嘌呤二核苷酸磷酸黄递酶（NADPH-d）、胆碱乙酰转移酶（ChAT）、胆囊收缩素（CCK）和胶质纤维酸性蛋白（GFAP）呈阳性染色。这些结果表明，新生儿期IH损伤后移植胎儿新皮质组织与运动功能缺损的改善有关，且移植组织表现出类似于正常新皮质的神经化学表型。鉴于其潜在的治疗用途，这种方法值得继续研究。
