Delayed administration of NGF reverses nerve injury induced central alterations of primary afferents.
We have examined whether delayed exogenous NGF administered to an axotomised peripheral nerve reverses the increased transganglionic choleragenoid (CTB) labelling in lamina II. Two, four, eight or 18 weeks after bilateral sciatic nerve section, NGF was applied unilaterally for an additional 2-week period to the transected nerve stump. The transganglionic choleragenoid labelling and substance P (SP) expression were determined and compared to the contralateral axotomised side in the spinal cord dorsal horn. Delayed NGF administration reversed the transganglionic choleragenoid labelling in lamina II when administered 2 or 18 weeks after the sciatic nerve lesion, but not at 4 or 8 weeks. There was also a clear recovery of SP on the axotomised, NGF-treated side 2 or 18 weeks after the sciatic nerve lesion, but not at the intermediate survival times. At the longer survival time, however, there was a recovery of SP regardless of NGF treatment. These results suggest that there is a critical window as to when NGF administration can be effective in reversing axotomy-induced changes in the spinal cord.
Siri
C R
CR
Department of Surgery, Karolinska Institutet, Huddinge Hospital, Sweden.
Shortland
P J
PJ
Grant
G
G
Olivius
N P
NP
D000344:Afferent Pathways / Q000187:drug effects* / Q000378:metabolism / Q000601:surgery; D000818:Animals; D019771:Axotomy; D002772:Cholera Toxin / Q000493:pharmacokinetics; D004334:Drug Administration Schedule; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D020932:Nerve Growth Factor / Q000494:pharmacology*; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology; D020671:Posterior Horn Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000187:drug effects* / Q000378:metabolism / Q000601:surgery; D013373:Substance P / Q000378:metabolism; D013997:Time Factors
D013373:Substance P; D002772:Cholera Toxin; D020932:Nerve Growth Factor