Intrathecal administration of nerve growth factor delays GAP 43 expression and early phase regeneration of adult rat peripheral nerve.
Whether nerve growth factor (NGF) promotes peripheral nerve regeneration in vivo, in particular in adults, is controversial. We therefore examined the effect of exogenous NGF on nerve regeneration and the expression of GAP 43 (growth-associated protein 43) in adult rats. NGF was infused intrathecally via an osmotic mini-pump, while control rats received artificial cerebrospinal fluid. Two days after the infusion was initiated, the right sciatic nerves were transected or crushed, and the animals allowed to survive for 3 to 11 days. The right DRG, the right proximal stump of the transected sciatic nerve, and the posterior horn of the spinal cord were examined by Western blotting, immunohistochemistry, and electron microscopy. GAP 43 immunoreactivity in the NGF-treated animals was significantly lower than in the aCSF-treated controls. Electron microscopy showed that the number of myelinated and unmyelinated axons decreased significantly in the NGF-treated rats as compared with the controls. These findings are indicative that exogenous NGF delayed GAP 43 induction and the early phase of peripheral nerve regeneration and supports the hypothesis that the loss of NGF supply from peripheral targets via retrograde transport caused by axotomy serves as a signal for DRG neurons to invoke regenerative responses. NGF administered intrathecally may delay the neurons' perception of the reduction of the endogenous NGF, causing a delay in conversion of DRG neurons from the normal physiological condition to regrowth state.
Hirata
Akira
A
Third Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, Japan.
Masaki
Toshihiro
T
Motoyoshi
Kazuo
K
Kamakura
Keiko
K
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D048429:Cell Size / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D007839:Functional Laterality / Q000502:physiology; D019922:GAP-43 Protein / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D007150:Immunohistochemistry; D008297:Male; D008854:Microscopy, Electron; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D020932:Nerve Growth Factor / Q000378:metabolism / Q000494:pharmacology*; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D020426:Sciatic Neuropathy / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D013373:Substance P / Q000378:metabolism; D014855:Wallerian Degeneration / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology
D019922:GAP-43 Protein; D013373:Substance P; D020932:Nerve Growth Factor