Expression of ATF3 and axonal outgrowth are impaired after delayed nerve repair.
BACKGROUND
A delay in surgical nerve repair results in impaired nerve function in humans, but mechanisms behind the weakened nerve regeneration are not known. Activating transcription factor 3 (ATF3) increases the intrinsic growth state of injured neurons early after injury, but the role of long-term changes and their relation to axonal outgrowth after a delayed nerve repair are not well understood. ATF3 expression was examined by immunohistochemistry in motor and sensory neurons and in Schwann cells in rat sciatic nerve and related to axonal outgrowth after transection and delayed nerve repair (repair 0, 30, 90 or 180 days post-injury). Expression of the neuronal cell adhesion molecule (NCAM), which is expressed in non-myelinating Schwann cells, was also examined.


RESULTS
The number of neurons and Schwann cells expressing ATF3 declined and the length of axonal outgrowth was impaired if the repair was delayed. The decline was more rapid in motor neurons than in sensory neurons and Schwann cells. Regeneration distances over time correlated to number of ATF3 stained neurons and Schwann cells. Many neurofilament stained axons grew along ATF3 stained Schwann cells. If nerve repair was delayed the majority of Schwann cells in the distal nerve segment stained for NCAM.


CONCLUSIONS
Delayed nerve repair impairs nerve regeneration and length of axonal outgrowth correlates to ATF3 expression in both neurons and Schwann cells. Mainly non-myelinating Schwann cells (NCAM stained) are present in distal nerve segments after delayed nerve repair. These data provide a neurobiological basis for the poor outcomes associated with delayed nerve repair. Nerve trunks should, if possible, be promptly repaired.
Saito
Harukazu
H
Department of Hand Surgery, Malmö University Hospital, Malmö, Sweden. haruka-z@fa2.so-net.ne.jp
Dahlin
Lars B
LB
D051700:Activating Transcription Factor 3 / Q000378:metabolism*; D000818:Animals; D001369:Axons / Q000378:metabolism / Q000502:physiology*; D005260:Female; D007150:Immunohistochemistry; D009186:Myelin Sheath / Q000378:metabolism / Q000502:physiology; D009413:Nerve Fibers, Myelinated / Q000378:metabolism / Q000502:physiology; D009416:Nerve Regeneration / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D019635:Neurosurgical Procedures; D051381:Rats; D017208:Rats, Wistar; D012583:Schwann Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D012584:Sciatic Nerve / Q000293:injuries / Q000378:metabolism / Q000503:physiopathology*; D013997:Time Factors
D051700:Activating Transcription Factor 3
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