The regeneration of injured axons can be modified by providing a favorable environment for axonal extension or by activating the nerve cell body. This proposal explores how sensory neurons are activated or conditioned by a peripheral nerve injury. The regrowth of crushed axons in a dorsal root is transganglionically accelerated by an additional injury to the corresponding peripheral nerve. Although this phenomenon could represent a reaction of individual neurons to """"""""pruning'' of their peripheral processes, a more complex cellular chain of events must also be considered. In retrograde response to transection of a major peripheral nerve, some neurons in sensory ganglia die and their satellite glial cells proliferate. The hypothesis being tested is that neuronal death and glial reaction within the ganglion activate nearby cell bodies of surviving neurons. To stimulate regeneration, a subpopulation of neurons will be killed by """"""""suicide transport"""""""" of an intraneurally injected toxin. To block enhancement following nerve injury, an antimitotic agent will be injected directly into the ganglion. Nerve growth factor (NGF) regulates some of the responses of sensory neurons to injury. Approximately one half of the primary sensory neurons in rat lumbar spinal ganglia have high-affinity receptors that can be visualized and quantified by radioautography on the tissue sections incubated with radioiodinated NGF. Radioautography for the NGF receptor will be correlated with histochemistry for other markers to characterize the subpopulation of sensory neurons that respond to NGF. The possibility is being explored that neurons depending on NGF for their survival might be selectively vulnerable to death after peripheral axotomy. The studies with NGF may help to understand this specific enhancement and to guide investigation of other growth factors that might be involved.
| 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 |
