Unknown events that benefit axonal regeneration are induced in primary sensory neurons by peripheral nerve injury. During the past three years, this consequence of peripheral axotomy has been shown to be mimicked by the presence of inflammatory cells in the doral root ganglion. In the first two experiments, inflammatory responses in the dorsal root ganglion of rats and mice will be examined after uncomplicated peripheral nerve transection. Macrophages will be visualized with immunohistochemistry and cytokine mRNAs will be measured by an RNase protection assay. mRNA for the neurotrophic agent basic fibroblast growth factor will also be studied. In four other experiments, possible actions of inflammation-associated growth factors on satellite cells and neurons in the dorsal root ganglion will be investigated. Mitosis of satellite glial cells will be studied by thymidine radioautography following injection of recombinant growth factors into the dorsal root ganglion. mRNA for the growth associated protein GAP- 43 will be measured by in situ hybridization to determine whether it is induced by inflammation and if so by which cytokines. Other in situ hybridizations will be performed in search of putative cytokine receptors on sensory neurons. Finally, the effect of fibroblast growth factor on the nerve cell body will be assessed with axonal regeneration in rat dorsal spinal roots as the test system. These experiments are intended to elucidate cellular and molecular interactions in the dorsal root ganglion that may stimulate regenerative behavior in sensory nerve cell bodies. In the long term, this information may suggest methods to enhance the characteristically sluggish responses to injury of neurons in the central nervous system.
Richardson, P M; Verge, V M (1987) Axonal regeneration in dorsal spinal roots is accelerated by peripheral axonal transection. Brain Res 411:406-8 |
Richardson, P M; Verge, V M (1986) The induction of a regenerative propensity in sensory neurons following peripheral axonal injury. J Neurocytol 15:585-94 |