Pharmacological inhibitors of epidermal growth factor receptor (ErbB1) attenuate the ability of CNS myelin to inhibit axonal regeneration. However, it has been claimed that such effects are mediated by off-target interactions. We have tested the role of ErbB1 in axonal regeneration by culturing neurons from ErbB1 knockout mice in the presence of various inhibitors of axonal regeneration: CNS my...

Traumatic spinal cord injury (SCI) results in a cascade of tissue responses leading to cell death, axonal degeneration, and glial scar formation, exacerbating the already hostile environment and further inhibiting axon regeneration. Overcoming these inhibitory cues and promoting axonal regeneration is one of the primary targets in developing a cure for SCI. Previously, we demonstrated that tran...

Members of the epidermal growth factor (EGF) family are frequently implicated in the injury response of the mammalian nervous system. Although this implication is supported by extensive molecular evidence, it is not underpinned by conclusive functional data. Recently, we found that expression of an EGF homolog from the pond snail Lymnaea stagnalis (L-EGF) is upregulated after axotomy in the adu...

We previously showed that motor nerves are superior to sensory nerves in promoting axon regeneration after spinal root avulsion. It is, however, impractical to use motor nerves as grafts. One potential approach to enhancing axonal regeneration using sensory nerves is to deliver trophic factors to the graft. Here, we examined the regulation of receptors for brain-derived neurotrophic factor, gli...

Adult CNS neurons exhibit a reduced capacity for growth compared to developing neurons, due in part to downregulation of growth-associated genes as development is completed. We tested the hypothesis that SnoN, an embryonically regulated transcription factor that specifies growth of the axonal compartment, can enhance growth in injured adult neurons. In vitro, SnoN overexpression in dissociated ...

Several experimental strategies have been employed to minimize tissue damage and to enhance axonal growth and regeneration after spinal cord injury. The transplantation of suitable cell types to provide an axonal growth substrate and the application of growth factors have been shown to augment morphological and sometimes functional recovery. In this review we discuss the use of neural stem cell...

Adult mammalian peripheral neurons have an intrinsic regrowth capacity in response to axonal injury. The induction of calcium ion (Ca2+) oscillations at an injured site is critical for the regulation of regenerative responses. In polarized neurons, distal axonal segments contain a well-developed endoplasmic reticulum (ER) network that is responsible for Ca2+ homeostasis. Although these characte...

After injury to the central nervous system (CNS) in adults, axonal regeneration is confined, in part, by the inhibitory factors in CNS myelin, including Nogo-A protein, myelin-associated glycoprotein (MAG) and oligodendrocyte myelin glycoprotein (OMGP). These proteins, all bind to the same neuronal glycosylphosphatidylinositol-anchored receptors (NgR), and transduce inhibitory signals to cells ...

Functional recovery is often poor despite the capacity for axonal regeneration in the peripheral nervous system and advances in microsurgical technique. Regeneration of axons in mixed nerve into inappropriate pathways is a major contributing factor to this failure. In this study, we use the rat femoral nerve model of transection and surgical repair to evaluate (1) the effect of nerve transectio...

The canonical Wnt/β-catenin pathway is a highly conserved signaling cascade that plays critical roles during embryogenesis. Wnt ligands regulate axonal extension, growth cone guidance and synaptogenesis throughout the developing central nervous system (CNS). Recently, studies in mammalian and fish model systems have demonstrated that Wnt/β-catenin signaling also promotes axonal regeneration in ...