Himes B T, Tessler A
Philadelphia VA Hospital, Pennsylvania.
J Comp Neurol. 1989 Jun 8;284(2):215-30. doi: 10.1002/cne.902840206.
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.(ABSTRACT TRUNCATED AT 400 WORDS)
尽管发育中的神经元更容易发生逆行性或跨神经元变性,但新生动物比成年动物从神经损伤中恢复的程度更大(肯纳德,1942年;戈德曼,1974年;普伦德加斯特和施特尔兹纳,1976年;布雷格曼和戈德伯格,1982年、1983年)。这种“婴儿损伤效应”背后的细胞机制尚未完全了解(布雷格曼和戈德伯格,1982年)。背根神经节(DRG)是一个很好的模型,可用于比较发育中的和成年的神经系统在轴突切断对细胞存活和细胞功能影响方面的情况。我们研究了成年和新生大鼠坐骨神经切断结扎后L5背根神经节神经元的存活情况,并使用定性和定量免疫细胞化学方法检查脊髓内P物质免疫反应性(SPIR)的变化。将小麦胚芽凝集素-辣根过氧化物酶(WGA-HRP)应用于成年或新生大鼠的坐骨神经后的逆行运输表明,正常L5背根神经节中70%的神经元投射到坐骨神经切断部位。在成年大鼠中,所有L5背根神经节神经元中有20%在术后10至60天死亡;在新生大鼠中,50%的神经元在5至10天死亡。这些结果表明,坐骨神经切断后,成年大鼠中30%的轴突切断神经元和新生大鼠中75%的轴突切断神经元死亡,并且新生大鼠中的神经元损失更快且更广泛。在新生大鼠进行背根切断术后,未观察到L5背根神经节中有细胞死亡,因此表明在这个发育阶段,背根神经节神经元的存活取决于外周而非中枢过程。成年和新生大鼠I层和II层中的SPIR均先降低然后恢复,但恢复的时间进程和程度不同。在成年大鼠中,术后10天时,手术同侧L5节段内侧部分的SPIR耗尽,并至少持续2个月保持耗尽状态。到1年时出现部分恢复,但即使在研究的最长存活时间(15个月)时仍未完全恢复。出生时存在于背角的SPIR在出生当天神经切断后4天,同侧I层和II层中减少。在30天至60天之间,手术同侧背角中SPIR的密度与对侧完整侧几乎没有区别,表明比成年大鼠恢复得更快且更完全。(摘要截取自400字)