A conditioning lesion enhances sympathetic neurite outgrowth.

Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, OH 44106-4975, USA.
Experimental Neurology (Impact Factor: 4.62). 09/2005; 194(2):432-43. DOI: 10.1016/j.expneurol.2005.02.023
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ABSTRACT Axonal regeneration can be influenced by a conditioning lesion (an axonal injury made prior to a second test lesion). Previously, sympathetic neurons in vivo were shown to respond to a conditioning lesion with decreased neurite outgrowth, in contrast to the enhanced outgrowth observed in all other peripheral neurons examined. The present experiments tested the effects of a conditioning lesion on neurite outgrowth in vitro from the superior cervical ganglion (SCG) and the impact of several factors on that response. Ganglia axotomized 1 week earlier and then explanted in Matrigel or collagen gel responded with a significant increase in neurite extension compared to sham-operated ganglia. A distal axotomy produced by unilateral removal of the salivary glands (sialectomy) caused an increase in neurite outgrowth similar to that of a proximal axotomy. These conditioning lesions induced both an increase in the rate of elongation, and, in the case of the proximally axotomized SCG, a shorter initial delay of outgrowth. The enhanced outgrowth following sialectomy was specific to the nerve containing the majority of axons projecting to the salivary glands, suggesting that the conditioning lesion effect is restricted to previously injured neurons. Deletion of the gene for leukemia inhibitory factor (LIF), a gene induced by axotomy, did not abolish the conditioning lesion effect in SCG explants or dissociated cell cultures. In conclusion, sympathetic neurons are capable of responding to a conditioning lesion with increased neurite outgrowth. The hypothesis that the neuronal cell body response to axotomy plays an important role in the conditioning lesion response is discussed.

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    ABSTRACT: Macrophages have been implicated in peripheral nerve regeneration for some time, supposedly through their involvement in Wallerian degeneration, the process by which the distal nerve degenerates after axotomy and is cleared by phagocytosis. Thus, in several studies in which macrophage accumulation in the distal nerve was reduced and Wallerian degeneration inhibited, regeneration was delayed. However, this interpretation ignores the more recent findings that macrophages also accumulate around axotomized cell bodies. The function of macrophage action at this second site has not been clear. In two mutant strains of mice, the slow Wallerian degeneration (Wld(s)) mouse and the chemokine receptor CCR2 knock-out mouse, we report that macrophage accumulation after axotomy was abolished in both the dorsal root ganglion (DRG) and the distal sciatic nerve. To measure neurite outgrowth, DRG neurons were given a conditioning lesion, and outgrowth was measured in vitro 7 d later in the absence of the distal nerve segment. The increased growth normally seen after a conditioning lesion did not occur or was reduced in Wld(s) or CCR2(-/-) mice. In the superior cervical ganglion (SCG), particularly in Wld(s) mice, macrophage accumulation was reduced but not abolished after axotomy. In SCG neurons from Wld(s) mice, the conditioning lesion response was unchanged; however, in CCR2(-/-) mice in which the effect on macrophage accumulation was greater, SCG neurite outgrowth was significantly reduced. These results indicate that macrophages affect neurite outgrowth by acting at the level of peripheral ganglia in addition to any effects they might produce by facilitation of Wallerian degeneration.
    Journal of Neuroscience 10/2013; 33(41):16236-16248. · 6.75 Impact Factor
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    ABSTRACT: Studies of neuronal regeneration require examination of the axons independently of their cell bodies. Several effective strategies have been deployed to compartmentalize long axons of the peripheral nervous system (PNS). However, current strategies to compartmentalize axons of the central nervous system (CNS) may be limited by physical damage to cells during tissue dissociation or slicing, perturbation of three-dimensional tissue architecture, or insufficient axonal tissue for biological analysis.
    Journal of Neuroscience Methods 05/2014; · 1.96 Impact Factor
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