Robust regeneration of adult sensory axons in degenerating white matter of the adult rat spinal cord
Robust regeneration of adult sensory axons in degenerating white matter of the adult rat spinal cord
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DOI：
10.1523/jneurosci.19-14-05810.1999
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发表时间：
1999-07-15
影响因子：
5.3
通讯作者：
Silver, J
中科院分区：
文献类型：
--
作者：
Davies, SJA;Goucher, DR;Silver, J
我们最近报道，通过使用一种新颖的微移植技术将微量分离的成年大鼠背根神经节神经元直接注射到成年大鼠中枢神经系统通路中，受到最小程度干扰的成年中枢神经系统白质可以支持成年轴突的再生（Davies等人，1997）。这种无创注射程序最大限度地减少了疤痕，并允许大量再生的成年轴突立即进入成年中枢神经系统神经胶质区域，在那里它们迅速延伸很长的距离。一个关键问题是，损伤后急性和慢性阶段（最多 3 个月）的白质退化是否仍能支持再生。为了研究这一点，我们将成年感觉神经元微移植到成年大鼠脊髓的退化白质中，距背柱严重损伤处几毫米。尽管与髓磷脂密切接触，但即使在经历暴发性华勒变性的白质内，供体感觉轴突在远离移植部位的两个方向上的再生也是强劲的。沿着它们的路线，重新生长的轴突将大量的侧支延伸到邻近的背角。然而，进入病变后，无力延伸的生长锥停止了，并在高浓度的反应性神经胶质基质中变得营养不良。我们的研究结果提供了令人信服的证据，证明成人中枢神经系统再生的主要环境障碍是直接在病变部位形成的分子屏障，并且神经胶质疤痕之外的退化白质具有比以前想象的更大的支持轴突再生的内在能力。
We have recently reported that minimally disturbed adult CNS white matter can support regeneration of adult axons by using a novel microtransplantation technique to inject minute volumes of dissociated adult rat dorsal root ganglion neurons directly into adult rat CNS pathways (Davies et al., 1997). This atraumatic injection procedure minimized scarring and allowed considerable numbers of regenerating adult axons immediate access to the adult CNS glial terrain where they rapidly extended for long distances. A critical question remained as to whether degenerating white matter at acute and chronic stages (up to 3 months) after injury could still support regeneration. To investigate this, we have microtransplanted adult sensory neurons into degenerating white matter of the adult rat spinal cord several millimeters vestral to a severe lesion of the dorsal columns. Regeneration of donor sensory axons in both directions away from the site of transplantation was robust even within white matter undergoing fulminant Wallerian degeneration despite intimate contact with myelin. Along their route, the regrowing axons extended large numbers of collaterals into the adjacent dorsal horn. However, after entering the lesion, the vapidly extending growth cones stopped and became dystrophic within high concentrations of reactive glial matrix. Our results offer compelling evidence that the major environmental impediment to regeneration in the adult CNS is the molecular barrier that forms directly at the lesion site, and that degenerating white matter beyond the glial scar has a far greater intrinsic ability to support axon regeneration than previously thought possible.