title: A novel and robust conditioning lesion induced by ethidium bromide.
abstract: Molecular and cellular mechanisms underlying the peripheral conditioning lesion remain unsolved. We show here that injection of a chemical demyelinating agent, ethidium bromide, into the sciatic nerve induces a similar set of regeneration-associated genes and promotes a 2.7-fold greater extent of sensory axon regeneration in the spinal cord than sciatic nerve crush. We found that more severe peripheral demyelination correlates with more severe functional and electrophysiological deficits, but more robust central regeneration. Ethidium bromide injection does not activate macrophages at the demyelinated sciatic nerve site, as observed after nerve crush, but briefly activates macrophages in the dorsal root ganglion. This study provides a new method for investigating the underlying mechanisms of the conditioning response and suggests that loss of the peripheral myelin may be a major signal to change the intrinsic growth state of adult sensory neurons and promote regeneration.
authors.affiliation: Neurobiology Section, Biological Sciences Division, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Edmund R
authors.initials: ER
authors.lastname: Hollis
authors.affiliation: Neurobiology Section, Biological Sciences Division, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Nao
authors.initials: N
authors.lastname: Ishiko
authors.affiliation: Neurobiology Section, Biological Sciences Division, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Kristine
authors.initials: K
authors.lastname: Tolentino
authors.affiliation: Harvard University, Cambridge, MA 02138, USA.
authors.forename: Ernest
authors.initials: E
authors.lastname: Doherty
authors.affiliation: Department of Pathology, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Rodriguez
authors.affiliation: Department of Pathology, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Nigel A
authors.initials: NA
authors.lastname: Calcutt
authors.affiliation: Neurobiology Section, Biological Sciences Division, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: yzou@ucsd.edu.
authors.forename: Yimin
authors.initials: Y
authors.lastname: Zou
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004996:Ethidium / Q000008:administration & dosage*; D005260:Female; D005727:Ganglia, Spinal / Q000187:drug effects / Q000502:physiology; D009409:Nerve Crush / Q000379:methods*; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344; D012584:Sciatic Nerve / Q000187:drug effects* / Q000293:injuries*
chemical_list: D004996:Ethidium
keywords: Conditioning lesion; Demyelination; Ethidium bromide; Inflammation; Spinal cord injury