QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, September 17, 2008, 28(38):9330-9341; doi:10.1523/JNEUROSCI.2488-08.2008

This Article Full Text Full Text (PDF) Supplemental Data Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Related articles in J. Neurosci. Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (6) Citing Articles via Google Scholar Google Scholar Articles by Horn, K. P. Articles by Silver, J. Search for Related Content PubMed PubMed Citation Articles by Horn, K. P. Articles by Silver, J.

 Previous Article  |  Next Article 

Development/Plasticity/Repair
Another Barrier to Regeneration in the CNS: Activated Macrophages Induce Extensive Retraction of Dystrophic Axons through Direct Physical Interactions

Kevin P. Horn,^1 * Sarah A. Busch,^1 * Alicia L. Hawthorne,¹ Nico van Rooijen,² and Jerry Silver¹

¹Department of Neurosciences, Case Western Reserve University, Cleveland, Ohio 44106, and ²Department of Molecular Cell Biology, Faculty of Medicine, Vrije Universiteit Medisch Centrum, Vrije Universiteit, 1081 BT Amsterdam, The Netherlands

Correspondence should be addressed to Prof. Jerry Silver, Department of Neurosciences, Case Western Reserve University, 2109 Adelbert Road, E-658, Cleveland, OH 44106. Email: jxs10{at}cwru.edu

Injured axons of the adult CNS undergo lengthy retraction from the initial site of axotomy after spinal cord injury. Macrophage infiltration correlates spatiotemporally with this deleterious phenomenon, but the direct involvement of these inflammatory cells has not been demonstrated. In the present study, we examined the role of macrophages in axonal retraction within the dorsal columns after spinal cord injury in vivo and found that retraction occurred between days 2 and 28 after lesion and that the ends of injured axons were associated with ED-1+ cells. Clodronate liposome-mediated depletion of infiltrating macrophages resulted in a significant reduction in axonal retraction; however, we saw no evidence of regeneration. We used time-lapse imaging of adult dorsal root ganglion neurons in an in vitro model of the glial scar to examine macrophage–axon interactions and observed that adhesive contacts and considerable physical interplay between macrophages and dystrophic axons led to extensive axonal retraction. The induction of retraction was dependent on both the growth state of the axon and the activation state of the macrophage. Only dystrophic adult axons were susceptible to macrophage "attack." Unlike intrinsically active cell line macrophages, both primary macrophages and microglia required activation to induce axonal retraction. Contact with astrocytes had no deleterious effect on adult dystrophic axons, suggesting that the induction of extensive retraction was specific to phagocytic cells. Our data are the first to indicate a direct role of activated macrophages in axonal retraction by physical cell–cell interactions with injured axons.

Key words: spinal cord injury; dystrophic; inflammation; growth cone; proteoglycan; immunosuppression

---

Received May 30, 2008; revised July 29, 2008; accepted Aug. 5, 2008.

Correspondence should be addressed to Prof. Jerry Silver, Department of Neurosciences, Case Western Reserve University, 2109 Adelbert Road, E-658, Cleveland, OH 44106. Email: jxs10{at}cwru.edu

Related articles in J. Neurosci.:

This Week in The Journal

J. Neurosci. 2008 28: i. [Full Text]  

This article has been cited by other articles:

				J. C. Gensel, S. Nakamura, Z. Guan, N. van Rooijen, D. P. Ankeny, and P. G. Popovich Macrophages Promote Axon Regeneration with Concurrent Neurotoxicity J. Neurosci., March 25, 2009; 29(12): 3956 - 3968. [Abstract] [Full Text] [PDF]

				The Neuroscientist Comments: Comments Neuroscientist, February 1, 2009; 15(1): 7 - 8. [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help