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[移植星形胶质细胞在中枢神经系统轴突再生中的作用]

[The role of transplanted astrocytes for the regeneration of CNS axons].

作者信息

Imaizumi T, Lankford K L, Kocsis J D, Hashi K

机构信息

Department of Neurosurgery, Hakodate Municipal Hospital, 1-10-1 Minato-cho, Hakodate, Hokkaido 041-0821, Japan.

出版信息

No To Shinkei. 2001 Jul;53(7):632-8.

Abstract

Long tract axons in the mammalian CNS do not normally regenerate for appreciable distance after they transected. But we reported transplantation of Schwann cells(SCs) or olfactory ensheathing cells induced regeneration of transected rat dorsal column (DC) axons and improved the conduction. Scar formation(gliosis), for which astrocytes(ACs) play an important role, may be one of strong and physical barriers for the regeneration of CNS axon. Oligodendrocyte and myelin associated protein or products also inhibit the regeneration of the axons, as chemical barriers. To investigate how effective the promotion or the reduction of scar or myelin formation may be for axonal regeneration, we transplanted AC into transected DCs, or radiated(X-ray) the DCs, and compared to normal DCs or regenerated DCs following by SC transplantation. DCs of adult rats were transected at Th 11 and transplanted with SCs(6 x 10(4)) of adult rats or ACs(6 x 10(4)) of neonatal rats. Five to six weeks later, the spinal cords were removed and pinned in a recording chamber, and compound action potentials (CAPs) along the DC through the transected lesion were recorded, to investigate conduction properties(conduction velocity and response after high frequency stimulations). Following transplantation of SCs or ACs, histological examination revealed regenerated axons with SC-like patterns of remyelination in transected DCs. X-ray irradiation did not enhance the regeneration of DC axons. SC transplantation improved the conduction properties of transected DCs and increased the number of regenerated axons, compared to transected DCs without cell transplantation. AC transplantation resulted in improvement of the conduction properties, but the number of regenerated axons was similar to that of transected DCs without the transplantation. X-ray irradiation (40 Gy) three days before DC transection and AC transplantation prevented the electrophysiological continuity of axons through the transected lesion. This evidence revealed that AC transplantation secondarily enhanced the regeneration of axons, probably endogeneous SCs of dorsal roots migrated into the transected lesion and enhanced the axonal regeneration.

摘要

哺乳动物中枢神经系统(CNS)中的长轴突在横断后通常不会再生很长的距离。但我们报道过,移植雪旺细胞(SCs)或嗅鞘细胞可诱导大鼠横断背柱(DC)轴突再生并改善传导。星形胶质细胞(ACs)在其中发挥重要作用的瘢痕形成(胶质增生),可能是中枢神经系统轴突再生的强大物理屏障之一。少突胶质细胞以及髓磷脂相关蛋白或产物作为化学屏障,也会抑制轴突再生。为了研究促进或减少瘢痕或髓磷脂形成对轴突再生的效果如何,我们将AC移植到横断的DC中,或对DC进行辐射(X射线),并与正常DC或SC移植后的再生DC进行比较。成年大鼠的DC在胸11水平横断,并移植成年大鼠的SCs(6×10⁴个)或新生大鼠的ACs(6×10⁴个)。五到六周后,取出脊髓并固定在记录室中,记录沿DC通过横断损伤部位的复合动作电位(CAPs),以研究传导特性(传导速度和高频刺激后的反应)。在移植SCs或ACs后,组织学检查显示横断的DC中有再生轴突,并伴有类似SC的髓鞘再生模式。X射线照射并未增强DC轴突的再生。与未进行细胞移植的横断DC相比,SC移植改善了横断DC的传导特性并增加了再生轴突的数量。AC移植导致传导特性有所改善,但再生轴突的数量与未移植的横断DC相似。在DC横断和AC移植前三天进行X射线照射(40 Gy)可阻止轴突通过横断损伤部位实现电生理连续性。这一证据表明,AC移植可继发增强轴突再生,可能是背根的内源性SCs迁移到横断损伤部位并增强了轴突再生。

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