This proposal is designed to begin to study the parameters of axonal sprouting induced by Nerve Growth Factor (NGF) and by spinal cord denervation. The methods will be ultrastructural quantitation of the myelinated and unmyelinated axons of appropriate nerves and roots, light microscopic quantitation of neurons and autoradiography. Preliminary data indicate that endogenous NGF is implicated in the sprouting of central processes of dorsal root ganglion neurons after spinal cord denervation at birth. Other preliminary evidence indicates that a small population of dorsal root ganglion neurons are labeled with radiolabeled-NGF after spinal cord injury suggesting that a specific group of neurons may sequester NGF after injury. Consequently the obectives of this proposal are: 1) to quantify the effects of nerve growth factor in the uninjured mammal by examination of specific neural pathways in rats treated with NGF or the antibody to NGF, 2) to quantify the involvements of NGF in the sprouting response of dorsal root ganglion neurons after spinal denervation by administering NGF or its antibody to rats with spinal damage, 3) to investigate the dorsal root ganglion neuron population that binds radiolabeled NGF after spinal cord denervation. Given that the amount of sprouting may be related to functional recovery and that endogenous NGF would seem to be implicated in the response to spinal cord denervation, the establishment of these parameters may lead to futher studies designed to test the clinical applicability of these manipulations.
