Reier P J, Stokes B T, Thompson F J, Anderson D K
Departments of Neurological Surgery, University of Florida College of Medicine, Gainesville 32610.
Exp Neurol. 1992 Jan;115(1):177-88. doi: 10.1016/0014-4886(92)90245-l.
This article reviews recent findings concerning the feasibility, basic neurobiology, and potential functional benefits of fetal CNS tissue grafts into acute and chronic lesions of the adult spinal cord. In the rat, neuro-anatomical observations suggest that transplants into resection cavities establish neuritic projections that could functionally reunite separated rostral and caudal segments of the host spinal cord. Furthermore, some complementary electrophysiological evidence has been obtained for synaptic connectivity between host and graft neurons. In these studies, extracellular single-unit activity was evoked in fetal spinal cord (FSC) transplants by stimulating host dorsal roots that had been juxtaposed to donor tissue at the time of transplantation. In other investigations, we examined whether grafts could also establish axonal projections to appropriate areas of gray matter in the chronically injured spinal cord. For this purpose, fetal serotoninergic (5-HT) neurons were injected caudal to complete spinal cord transections that had been made 1-3 months earlier. Immunocytochemistry revealed that these cells projected their axons into gray matter regions normally innervated by bulbospinal 5-HT neurons. To investigate transplantation in a more clinically relevant lesion model, a third group of experiments involved injection of dissociated cell suspensions into acute [less than 24 h postinjury (p.i.)]), subchronic (7-10 days p.i), and chronic (greater than or equal to one month, p.i.) contusion lesions. Such grafts routinely filled areas that otherwise would have been regions of cavitation extending rostral-caudal distances of approximately 7 mm. FSC transplants in such injuries also appeared to influence some aspects of motoneuron excitability and hindlimb locomotion. More recent studies of the cat spinal cord have extended these findings in the rat by showing long-term survival (greater than 2 years) of fetal CNS allografts in recipients with either subtotal transection or compression lesions. Preliminary studies of connectivity have also shown host-graft projection patterns similar to those seen in the rat. Behavioral analyses are currently underway to examine the effects of fetal grafts in cats with chronic postcompression lesions. These observations in the rat and cat are discussed in the general context of basic biological and clinical issues relevant to the long-term objective of promoting functional improvement in the damaged spinal cord.
本文综述了有关将胎儿中枢神经系统（CNS）组织移植到成年脊髓急性和慢性损伤部位的可行性、基础神经生物学以及潜在功能益处的近期研究结果。在大鼠中，神经解剖学观察表明，移植到切除腔中的组织可建立神经突投射，从而在功能上使宿主脊髓分离的头端和尾端节段重新连接。此外，还获得了一些关于宿主与移植神经元之间突触连接的补充电生理证据。在这些研究中，通过刺激在移植时与供体组织相邻的宿主背根，在胎儿脊髓（FSC）移植组织中诱发细胞外单单位活动。在其他研究中，我们研究了移植组织是否也能在慢性损伤的脊髓中向灰质的适当区域建立轴突投射。为此，在1 - 3个月前完成全横断脊髓损伤的尾侧注射胎儿5 -羟色胺能（5 - HT）神经元。免疫细胞化学显示，这些细胞将其轴突投射到通常由延髓脊髓5 - HT神经元支配的灰质区域。为了在更具临床相关性的损伤模型中研究移植，第三组实验涉及将解离的细胞悬液注射到急性（损伤后不到24小时）、亚慢性（损伤后7 - 10天）和慢性（损伤后大于或等于1个月）挫伤性损伤部位。此类移植组织通常填充了原本会形成空洞的区域，这些空洞向头尾方向延伸的距离约为7毫米。在这类损伤中进行FSC移植似乎也会影响运动神经元兴奋性和后肢运动的某些方面。最近对猫脊髓的研究扩展了在大鼠中的这些发现，表明在患有部分横断或压迫性损伤的受体中，胎儿CNS同种异体移植可长期存活（超过2年）。连接性的初步研究也显示出与在大鼠中所见相似的宿主 - 移植投射模式。目前正在进行行为分析，以研究胎儿移植组织对患有慢性压迫性损伤的猫的影响。本文在与促进受损脊髓功能改善这一长期目标相关的基础生物学和临床问题的总体背景下，对大鼠和猫的这些观察结果进行了讨论。
