Transplantation of fetal neocortex ameliorates sensorimotor and locomotor deficits following neonatal ischemic-hypoxic brain injury in rats

Transplantation of fetal neocortex ameliorates sensorimotor and locomotor deficits following neonatal ischemic-hypoxic brain injury in rats
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DOI:
10.1006/exnr.1997.6596
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发表时间:
1997-10-01
影响因子:
5.3
通讯作者:
Low, WC
Low, WC
中科院分区:
医学2区
文献类型:
--
作者:
Jansen, EM;Solberg, L;Low, WC

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新生儿缺血性脑损伤可导致大脑皮质和皮质下区域的变性,并与神经功能缺损相关。在缺血性脑损伤的情况下恢复功能的一种方法是使用神经移植来修复受损的连接。这种方法已被证明可以重建神经回路并改善新生儿感觉运动皮层损伤模型中的相关运动缺陷。在这项研究中,我们利用Rice等人的新生儿缺血-缺氧(IH)脑损伤啮齿动物模型(26)来评估移植胎儿新皮质组织是否可以在整个发育过程中和成年后的感觉运动和运动能力测试中促进功能恢复,我们发现,在IH损伤后3天接受新皮质移植的动物在两项运动指标上表现得明显优于成年动物。能力,Rota-nod跑步机和阿扑吗啡诱导的旋转,比对照组动物接受假移植后IH损伤。移植后10-12周,72%的动物可识别移植物。组织化学研究表明,虽然移植组织没有建立正常的皮质细胞结构,但移植物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)和胶质细胞酸性蛋白(GFAP)进行了染色,这些结果表明,在新生儿期IH损伤后移植胎儿新皮质组织与改善运动缺陷有关,组织表现出类似于正常新皮层的神经化学表型。鉴于潜在的治疗用途,这种方法值得继续研究。(C)北京:科学出版社.
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 (26) 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-nod 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. (C) 1997 Academic Press.