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The Role of Schwann Cells in Maintaining Regeneration of Sensory Axons in the Rat

 
Abstract:

This post is also available in: English Slovenščina (Slovenian)

Satisfactory regeneration of axons after crush injury of periferal nerve is supported by pro­liferating Schwann cells (SC) in the distal stump and their basal laminae (BL). SC secrete diffusable growth-promoting substances, whereas basal laminae provide a good growth substratum within the neurilemmal tubes. The results of previous studies of the relative impor­tance of diffusable growth-promoting substances and growth substratum are partly contra­dictory. A recent study showed that sensory axons regenerating through the acellular distal nerve segment elongated fairly rapidly during the first week after axonotmesis, but then cea­sed to grow. The leading axons retracted towards the site of axonotmesis. Subsequent elon­gation was possible only with concurrent migration of SC from the proximal stump. Previous experiments indicated that degeneration of growth substratum in the absence of Schwann cells could be responsible for the cessation of axonal growth. The objective of the study was to examine the following hypotheses: that cessation of axonal growth and retraction of sen­sory axons during the second week of regeneration in the absence of cell support is a con­sequence of an unfavourable microenviroment of the regenerating axons and is not due to permanent »exhaustion« of the neuron cell body; that, if an adequate growth substratum is maintained, axons continue to grow during the second week even in the absence of SC; and that elongation of axons can be maintained during prolonged regeneration through the acel­lular distal nerve segment by providing diffusable growth promoting substances of SC, even though the growth substratum is partly degenerated. In this study, a rat sural nerve was crus­hed. In the first group of animals, cells in the distal stump were killed by freezing the entire distal segment at once. In the second experimental group, only 10 or 15 mm long segment of the nerve adjacent to the crush site was frozen in order to leave the cells distally alive.  Nerves in the third group of animals were frozen twice, with an interval of four days in between. The second freezing was applied to the nerve segment, distally to the first. In the fourth group, a nerve sandwich was composed of a frozen sural nerve wrapped in a degenerated segment of the peroneal nerve. The elongation rate of regenerating axons was monitored by nerve pinch test. Axons in the nerve cross-sections were demonstrated by imunnohistochemical staining of neurofilaments. We confirmed that rapid initial growth of sensory axons through a completely acellular distal nerve segment stopped after eight days. Thereafter, the leading axons began to retract. When the regeneration of axons through 10 or 15 mm long acellular segments was examined, there was no reduction in the elongation rate. The growth of axons along successivly frozen nerve segments did not stop during the second week, although it did slow down. The elongation of axons through the nerve sandwich was slowed down during the second week, but it did not stop. Cessation of axon growth through an acellular distal nerve segment in a crushed nerve is a consequence of an unfavourable microenviroment of the regenerating axons. By maintaining good growth substratum, growth can be sustained, even though viable cells are not present. By providing diffusable growth promo­ting factors (secreted by SC), we enabled the axons to elongate during prolonged regenera­tion even in the presence of partly degenerated growth substratum

Authors:
Gril Iztok, Jug Marko

Keywords:
cells, nerve regeneration, peripheral nerve - injuries, trophic factors

Cite as:
Med Razgl. 2000; 39: 135–49.

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