Combined fetal neural transplantation and nerve growth factor infusion: Effects on neurological outcome following fluid-percussion brain injury in the rat
Combined fetal neural transplantation and nerve growth factor infusion: Effects on neurological outcome following fluid-percussion brain injury in the rat
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DOI：
10.3171/jns.1996.84.4.0655
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发表时间：
1996-04-01
影响因子：
4.1
通讯作者：
McIntosh, TK
中科院分区：
文献类型：
--
作者：
Sinson, G;Voddi, M;McIntosh, TK
本研究的目的是评估胚胎神经移植和不输注神经营养因子的创伤性脑损伤大鼠的组织学和行为的影响，使用临床相关的模型，侧液压冲击脑损伤。成年雄性Sprague-Dawley大鼠接受中度（2.1-2.3 aim）的侧向液压冲击脑损伤。损伤后24小时，将切碎的胎儿皮质移植物（E16）立体定向移植到损伤空腔形成部位（32只大鼠）。10只对照动物接受盐水注射。第三组29只接受移植的动物也接受了微量渗透泵的放置（移植后立即），在实验期间连续将神经生长因子（NGF）直接注入移植物放置区域。第四组8只动物接受了已分离并置于悬浮液中的胎儿皮质细胞移植。在损伤后72小时、1周和2周评价动物的认知功能（使用Morris水迷宫）、创伤后运动功能障碍和移植存活率和形态学（使用Nissl和改良的Palmgren银染色技术）。在65.6%的动物中观察到全组织移植的稳健存活，并且在接受NGF输注的动物中没有增加。接受细胞悬液移植的动物没有存活的移植物。在2周的评估中，接受移植的脑损伤动物与对照组相比表现出显着的认知改善。与受伤的对照组相比，接受NGF和移植的动物在所有评估时间都有显着改善的记忆评分，并且与72小时和1周评估时单独接受移植的动物相比。神经运动功能评分显着改善动物接受移植单独和那些接受移植与神经生长因子输注。组织学评价表明，移植细胞的分化，减少周围移植物与对照动物相比，神经胶质瘢痕形成，以及桥接移植物和宿主之间的界面的神经元纤维的存在。这项研究表明，胚胎皮层细胞移植到成年大鼠损伤的皮层可以改善创伤后的认知和运动功能，并与受损的宿主脑相互作用。
This study was designed to evaluate the histological and behavioral impact of fetal neural transplantation with and without neurotrophin infusion in rats subjected to traumatic brain injury using a clinically relevant model of lateral fluid-percussion brain injury. Adult male Sprague-Dawley rats received lateral fluid-percussion brain injury of moderate severity (2.1-2.3 aim). Twenty-four hours after injury, minced fetal cortical grafts (E16) were stereotactically transplanted into the site of injury cavity formation (in 32 rats). Ten control animals received injections of saline. A third group of 29 animals that received transplants also underwent placement of a miniosmotic pump (immediately after transplantation) to continuously infuse nerve growth factor (NGF) directly into the region of graft placement for the duration of the experiment. A fourth group of eight animals underwent transplantation of fetal cortical cells that had been dissociated and placed in suspension. Animals were evaluated at 72 hours, 1 week, and 2 weeks after injury for cognitive function (using the Morris water maze), posttraumatic motor dysfunction, and transplant survival and morphology (using Nissl and modified Palmgren's silver staining techniques). Robust survival of whole-tissue transplants was seen in 65.6% of animals and was not increased in animals receiving NGF infusion. Animals receiving transplants of cell suspension had no surviving grafts. Brain-injured animals receiving transplants showed significant cognitive improvements compared with controls at the 2-week evaluation. Significantly improved memory scores were seen at all evaluation times in animals receiving both NGF and transplants compared with injured controls and compared with animals receiving transplants alone at the 72-hour and 1-week evaluations. Neurological motor function scores were significantly improved in animals receiving transplants alone and those receiving transplants with NGF infusion. Histological evaluation demonstrated differentiation of grafted cells, decreased glial scarring around transplants when compared with control animals, and the presence of neuronal fibers bridging the interface between graft and host. This study demonstrates that fetal cortical cells transplanted into the injured cortex of the adult rat can improve both posttraumatic cognitive and motor function and interact with the injured host brain.