Death of some dorsal root ganglion neurons and plasticity of others following sciatic nerve section in adult and neonatal rats.
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)
Himes
B T
BT
Philadelphia VA Hospital, Pennsylvania.
Tessler
A
A
D000375:Aging / Q000502:physiology*; D000818:Animals; D002452:Cell Count; D002470:Cell Survival; D005727:Ganglia, Spinal / Q000166:cytology / Q000502:physiology*; D006735:Horseradish Peroxidase; D007150:Immunohistochemistry; D009473:Neuronal Plasticity; D051381:Rats; D011919:Rats, Inbred Strains / Q000502:physiology*; D012584:Sciatic Nerve / Q000166:cytology / Q000502:physiology*; D013373:Substance P / Q000378:metabolism; D018998:Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate; D014909:Wheat Germ Agglutinins
D018998:Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate; D014909:Wheat Germ Agglutinins; D013373:Substance P; D006735:Horseradish Peroxidase