An in vitro model of adult mammalian nerve repair.

Mark McIntosh,'s picture
PubMed URL: 
http://www.ncbi.nlm.nih.gov/pubmed/19464291
Author: 
Brushart TM
Author List: 
Vyas A
Li Z
Aspalter M
Feiner J
Hoke A
Zhou C
O'Daly A
Abdullah M
Rohde C
Brushart TM
Journal: 
Exp Neurol
PubMed ID: 
19464291
Pagination: 
112-8
Volume: 
223
Issue: 
1
Abstract: 
The role of pathway-derived growth factors in the support of peripheral axon regeneration remains elusive. Few appropriate knock-out mice are available, and gene silencing techniques are rarely 100% effective. To overcome these difficulties, we have developed an in vitro organotypic co-culture system that accurately models peripheral nerve repair in the adult mammal. Spinal cord sections from P4 mice that express YFP in their neurons are used to innervate segments of P4 peripheral nerve. This reconstructed ventral root is then transected and joined to a nerve graft. Growth of axons across the nerve repair and into the graft can be imaged repeatedly with fluorescence microscopy to define regeneration speed, and parent neurons can be labeled in retrograde fashion to identify contributing neurons. Nerve graft harvested from adult mice remains viable in culture by both morphologic and functional criteria. Motoneurons are supported with GDNF for the first week in culture, after which they survive axotomy, and are thus functionally adult. This platform can be modified by using motoneurons from any genetically modified mouse that can be bred to express XFP, by harvesting nerve graft from any source, or by treating the culture systemically with antibodies, growth factors, or pathway inhibitors. The regeneration environment is controlled to a degree not possible in vivo, and the use of experimental animals is reduced substantially. The flexibility and control offered by this technique should thus make it a useful tool for the study of regeneration biology.
Published Date: 
May, 2010

Appointments & Referrals

FIND A SPECIALIST

Publications

Read inspiring stories, news and updates about the Institute's patient care, research, special education, professional training, and community programs.

 

Resource Finder

 

A free resource that provides access to information and support for individuals and families living with developmental disabilities.