Axonal outgrowth is associated with increased ERK 1/2 activation but decreased caspase 3 linked cell death in Schwann cells after immediate nerve repair in rats.
BACKGROUND
Extracellular-signal regulated kinase (ERK1/2) is activated by nerve damage and its activation precedes survival and proliferation of Schwann cells. In contrast, activation of caspase 3, a cysteine protease, is considered as a marker for apoptosis in Schwann cells. In the present study, axonal outgrowth, activation of ERK1/2 by phosphorylation (p-ERK 1/2 ) and immunoreactivity of cleaved caspase 3 were examined after immediate, delayed, or no repair of transected rat sciatic nerves.


RESULTS
Axonal outgrowth, detected by neurofilament staining, was longer after immediate repair than after either the delayed or no repair conditions. Immediate repair also showed a higher expression of p-ERK 1/2 and a lower number of cleaved caspase 3 stained Schwann cells than after delayed nerve repair. If the transected nerve was not repaired a lower level of p-ERK 1/2 was found than in either the immediate or delayed repair conditions. Axonal outgrowth correlated to p-ERK 1/2, but not clearly with cleaved caspase 3. Contact with regenerating axons affected Schwann cells with respect to p-ERK 1/2 and cleaved caspase 3 after immediate nerve repair only.


CONCLUSIONS
The decreased regenerative capacity that has historically been observed after delayed nerve repair may be related to impaired activation of Schwann cells and increased Schwann cell death. Outgrowing axons influence ERK 1/2 activation and apoptosis of Schwann cells.
Department of Orthopedic Surgery, National Defense Medical College, Saitama, Japan.
Yoshifumi
Y
Tsuda
Martin
M
Kanje
Lars B
LB
Dahlin
D000818:Animals; D001369:Axons / Q000201:enzymology* / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism*; D016923:Cell Death / Q000502:physiology; D004789:Enzyme Activation / Q000502:physiology; D005260:Female; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009416:Nerve Regeneration / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012583:Schwann Cells / Q000201:enzymology* / Q000473:pathology; D020426:Sciatic Neuropathy / Q000201:enzymology* / Q000473:pathology
D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D053148:Caspase 3
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