DEATH OF SOME DORSAL-ROOT GANGLION NEURONS AND PLASTICITY OF OTHERS FOLLOWING SCIATIC-NERVE SECTION IN ADULT AND NEONATAL RATS
DEATH OF SOME DORSAL-ROOT GANGLION NEURONS AND PLASTICITY OF OTHERS FOLLOWING SCIATIC-NERVE SECTION IN ADULT AND NEONATAL RATS
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DOI：
10.1002/cne.902840206
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发表时间：
1989-06-08
影响因子：
2.5
通讯作者：
TESSLER, A
中科院分区：
文献类型：
--
作者：
HIMES, BT;TESSLER, A
新生动物从神经损伤中恢复的程度比成年动物大，尽管发育中的神经元更容易发生逆行或跨神经元变性（肯纳德，“42;戈德曼，”74;普伦德加斯特和施特尔茨纳，“76;布雷格曼和戈德伯格，”82，“83）。这种“婴儿损伤效应”的细胞机制尚未完全了解（Bregman和Goldberger，'82）。背根神经节（DRG）是一个很好的模型，其中比较发育和成人神经系统的影响，轴突切断对细胞存活和细胞功能。我们研究了成年和新生大鼠坐骨神经节段结扎后L5 DRG神经元的存活情况，并采用定性和定量免疫细胞化学方法检测脊髓内P物质免疫反应性（SPIR）的变化。应用小麦胚芽凝集素-辣根过氧化物酶（WGA-HRP）逆行运输成年或新生大鼠坐骨神经表明，70%的神经元在正常的L5背根神经节的项目进入坐骨神经横断的网站。在成人中，20%的L5 DRG神经元在术后10至60天死亡;在新生儿中，50%的神经元在术后5至10天死亡。这些结果表明，30%的成年人和75%的新生儿轴突切断神经元坐骨神经节后死亡，神经元损失是更迅速，更广泛的新生儿。背根切断后，新生儿L5背根节中未观察到细胞死亡，这表明在这个发育阶段，背根节神经元的存活取决于外周突起，而不是中央突起。成人和新生儿手术后第I、II层SPIR均先降低后恢复，但恢复的时间和程度不同。在成人中，SPIR在手术后10天在同侧L5节段的内侧部分耗尽，并保持耗尽至少2个月。1年时部分恢复，但即使在研究的最长生存时间（15个月）仍不完全。SPIR，这是目前在背角在出生时，减少在同侧椎板I和II的4天后，神经节在出生当天。30天和60天之间，SPIR的密度在同侧的背角手术变得几乎无法区分对侧，完整的一面，这表明一个更快，更完整的恢复比成人。SPIR染色所占的面积仍然小于未手术侧所见的面积，因此表明去传入背角终末野发育不完全或异常。在SPIR恢复后重新切割坐骨神经耗尽了成人和新生儿中恢复的SPIR，表明在两组中恢复主要是由于DRG神经元在其轴突的初始横断中存活。结果表明，在发育中的动物中，切断坐骨神经后存活的DRG神经元的25%可以恢复正常的P物质（SP）向背角投射的模式和密度。因此，未成熟的DRG神经元似乎更有可能在轴突切断后死亡，但与轴突切断的成熟DRG细胞相比，那些存活的神经元能够进行强大的解剖和生化重组。
Newborn animals recover from neurological injury to a greater extent than adults in spite of the greater vulnerability of developing neurons to retrograde or transneuronal degeneration (Kennard, ''42; Goldman, ''74; Prendergast and Stelzner, ''76; Bregman and Goldberger, ''82, ''83). The cellular mechanisms underlying this "infant lesion effect" are incompletely understood (Bregman and Goldberger, ''82). The dorsal root ganglion (DRG) is an excellent model in which to compare the developing and adult nervous system with respect to the effects of axotomy on cell survival and cellular function. We studied the survival of L5 DRG neurons after section-ligation of the sciatic nerve of adult and neonatal rats and used qualitative and quantitative immunocytochemical methods to examine changes in intraspinal substance P immunoreactivity (SPIR). Retrograde transport of wheatgerm agglutinin-horseradish (WGA-HRP) peroxidase applied to the sciatic nerve of adult or neonatal rats demonstrated that 70% of the neurons in the normal L5 DRG project into the sciatic nerve at the site of transection. In adults 20% of all L5 DRG neurons died between 10 and 60 days postoperative; in newborns 50% of the neurons died between 5 and 10 days. These results indicate that 30% of axotomized neurons in adults and 75% in neonates die after sciatic nerve section and that neuron loss is both more rapid and more extensive in neonates. No cell death was observed in the L5 DRG of neonates after dorsal rhizotomy, thus suggesting that at this stage of development the survival of DRG neurons depends on the peripheral but not the central process. SPIR in laminae I and II of both adult and newborn operates decreased and then recovered, but the time course and extent of the recovery differ. In adults SPIR was depleted in the medial portion of the L5 segment ipsilateral to surgery by 10 days postoperative and remained depleted for at least 2 months. By 1 year partial recovery occurred, but remained incomplete even at the longest survival time studied (15 months). SPIR, which is present in the dorsal horn at birth, was diminished in ipsilateral laminae I and II by 4 days after nerve section on the day of birth. Between 30 days and 60 days, the density of SPIR in the dorsal horn ipsilateral to surgery became virtually indistinguishable from that on the contralateral, intact side, suggesting a more rapid and complete recovery than in adults. The area occupied by SPIR staining remained smaller than that seen on the unoperated side, thus suggesting incomplete or abnormal development of the terminal field in the deafferented dorsal horn. Recutting the sciatic nerve after SPIR recovery depleted the recovered SPIR in both adults and neonates, indicating that in both groups recovery was largely due to DRG neurons that had survived initial transection of their axons. The results indicate that in developing animals 25% of the normal numbers of DRG neurons that survive sciatic nerve section can restore the normal pattern and density of the substance P (SP) projection to the dorsal horn. Immature DRG neurons, therefore, appear to be more likely to die after axotomy, yet those that survive are capable of robust anatomical and biochemical reorganization in comparison to axotomized mature DRG cells.