Abstract
BackgroundThe growth-associated protein GAP-43 plays a crucial role in axonal regeneration in injured neurons.MethodsWe have used immunohistochemistry to investigate the expression of GAP-43 in spinal motoneurons during nerve reconstruction following root avulsion in the neonatal and adult rats.ResultsFollowing the injury, GAP-43-immunoreactivity (IR) could be found in adult avulsed motoneurons as early as 1 day, increased from 3 to 7 days and reached a maximal level at 2 weeks post-injury. The up-regulation of GAP-43 in adult avulsed motoneurons was accompanied with the axonal regeneration indicated by numerous regenerating motor axons entering the reimplanted ventral root and nerve. In contrast, GAP-43-IR could not be found in the neonatal avulsed motoneurons at any examined post-injury time points. This failure of up-regulation of GAP-43 was coincident with no axonal regeneration in the reimplanted nerve in the neonatal rats.ConclusionClose association of GAP-43 expression and capacity of regeneration in reimplanted spinal nerve of avulsed motoneurons suggests that GAP-43 is a potential therapeutic target for treatment of root avulsion of brachial plexus.
Highlights
The growth-associated protein GAP-43 plays a crucial role in axonal regeneration in injured neurons
Avulsed motoneurons in neonatal rats are unable to regenerate into a peripheral nerve (PN) graft [12], which indicates that intrinsic neuronal factors determine the regenerative capabilities
Brain-derived neurotrophic factor (BDNF) but not neurotrophin-3 (NT-3) was found to increase the number of axotomized rubrospinal tract neurons that regenerated into grafts of sciatic nerve implanted into the spinal cord at the level of spinal transaction, correlating with the stimulation of GAP-43 expression after application of brain-derived neurotrophic factor (BDNF) but not of NT-3
Summary
The growth-associated protein GAP-43 plays a crucial role in axonal regeneration in injured neurons. Regenerating neurons in mammalian peripheral nervous system (PNS) undergo a variety of changes in gene expression, for example, the prominent upregulation of growth-associated proteins [13,14]. This regenerationassociated gene (RAG) expression is believed to enhance the growth potential of injured neurons. Brain-derived neurotrophic factor (BDNF) but not neurotrophin-3 (NT-3) was found to increase the number of axotomized rubrospinal tract neurons that regenerated into grafts of sciatic nerve implanted into the spinal cord at the level of spinal transaction, correlating with the stimulation of GAP-43 expression after application of BDNF but not of NT-3. The potential role of such expression for axonal regeneration of avulsed motoneurons after root avulsion was discussed
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