The experiments that comprise this application test the hypothesis that distinct subsets of primary afferent neurons respond differently to transection of a peripheral nerve in early postnatal life. Peripheral nerve damage in a newborn produces a number of changes in the primary afferent innervation of the periphery and the spinal cord and/or brainstem. These include the death of some axotomized ganglion cells and axonal regeneration (either accurately or inaccurately) by others, peripheral and central collateral sprouting by undamaged primary afferents, and reorganization of the projections of both damaged and undamaged axons at the level of the ganglion. Primary afferent neurons can be distinguished by a variety of markers including birthdate, peptide phenotype, the presence of different cell surface antigens, and binding of different lectins. We will use several such markers to define the effects of neonatal transection of the rat's infraorbital nerve (ION) upon 4 distinct subsets of trigeminal (V) ganglion cells: those that synthesize substance P, those that synthesize somatostatin, those that bind the lectin Bandeiraea simplicifolia-I (BS-I), and those that are recognized by the monoclonal antibody RT97, a marker for neurofilament [3H]-thymidine labelling. We will use these markers in conjunction with retrograde tracing, sequential multiple labelling, and intracellular recording and tracer injection to determine the extent to which members of each of the cell classes listed above: 1) die as a result of neonatal axotomy, 2) regenerate accurately to the periphery after such damage, 3) engage in peripheral collateral sprouting after injury to other V axons, and 4) reorganize their peripheral projections at the level of the V ganglion after damage to their own axons or those of other V primary afferents. In a final series of experiments, we will evaluate the role that nerve growth factor may play in accuracy of regeneration of damaged axons and peripheral collateral sprouting by undamaged fibers by depriving rats of NGF after neonatal ION transection. Information about the extent to which distinct subclasses nerve damage may ultimately permit independent modulation of each of these types of reorganization.

Project Start
Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Saint Louis University
Department
Type
DUNS #
City
Saint Louis
State
MO
Country
United States
Zip Code
63103
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