Blöchlinger S, Weinmann O, Schwab M E, Thallmair M
Brain Research Institute, University of Zurich and Swiss Federal Institute of Technology-Zurich, CH-8057 Zurich, Switzerland.
J Comp Neurol. 2001 May 7;433(3):426-36. doi: 10.1002/cne.1150.
Regeneration and compensatory sprouting are limited after lesions in the mature mammalian central nervous system in contrast to the developing central nervous system (CNS). After neutralization of the growth inhibitor Nogo-A, however, massive sprouting and rearrangements of fiber connections occurred after unilateral pyramidal tract lesions in adult rats: Corticofugal fibers from the lesioned side crossed the midline of the brainstem and innervated the contralateral basilar pontine nuclei. To determine whether these newly sprouted fibers formed synaptic contacts, we analyzed the corticofugal fibers in the basilar pontine nuclei contralateral to the lesion by light and electron microscopy 2 weeks after pyramidotomy and treatment with the Nogo-A-inhibiting monoclonal antibody IN-1 (mAb IN-1). The mAb IN-1, but not a control antibody, led to structural changes in the basilar pons ipsilateral and contralateral to the lesion site. Fibers sprouted across the pontine midline and terminated topographically. They established asymmetric synaptic contacts with the characteristics of normal corticopontine terminals. These results show that adult CNS fibers are able to sprout and to form new synaptic contacts after a lesion when a growth-permissive microenvironment is provided.
与发育中的中枢神经系统（CNS）相比，成熟哺乳动物中枢神经系统损伤后的再生和代偿性发芽是有限的。然而，在中和生长抑制因子Nogo-A后，成年大鼠单侧锥体束损伤后发生了大量的发芽和纤维连接重排：损伤侧的皮质离心纤维穿过脑干中线并支配对侧基底桥核。为了确定这些新发芽的纤维是否形成突触联系，我们在锥体切断术并用Nogo-A抑制单克隆抗体IN-1（mAb IN-1）处理2周后，通过光学显微镜和电子显微镜分析了损伤对侧基底桥核中的皮质离心纤维。mAb IN-1而非对照抗体导致损伤部位同侧和对侧基底桥的结构变化。纤维穿过脑桥中线发芽并按拓扑结构终止。它们建立了具有正常皮质桥脑终末特征的不对称突触联系。这些结果表明，当提供允许生长的微环境时，成年中枢神经系统纤维在损伤后能够发芽并形成新的突触联系。
