The studies are intended to examine certain cellular and extracellular factors which may influence the degree of axonal regeneration within the central nervous sytem (CNS) of vertebrates. The hypothesis to be tested is whether the cellular constituents of the CNS in the frog (such as glial cells and their reaction to injury) facilitate regeneration in some instances and limit it in others. One objective of the research is to make a detailed examination of the influence of apparently adverse environmental factors on axonal outgrowth from cells normally capable of extensive regeneration after axotomy. This will be done by introducing a population of CNS axons with known regenerative ability (retinal ganglion cell axons) into the spinal cord where axonal regeneration is reported to be minimal. Embryonic eye primordia will be transplanted to the flank region of host embryos and axons from transplanted eyes will grow into and extend along spinal cord pathways. When the hosts reach adult age, the spinal cord will be transected to sever the optic nerve fibers and the ability of these axons to regenerate through or around the cord lesion will be studied by anterograde HRP filling to label individual regenerating axons and by electron microscopy. A second objective is to determine the influence on axonal regeneration of membrane-bound glycoproteins (nerve cell adhesion molecules - NCAMs). The ultrastructural location of these molecules on axons, growth cones and CNS glia will be determined using immunocytochemical localization and electron microscopy. The suspected role of these proteins in axonal regeneration will be examined by determining if antibodies directed against the proteins block optic nerve axon regeneration and prevent regenerative synaptogenesis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS020060-06
Application #
3400270
Study Section
Neurology B Subcommittee 1 (NEUB)
Project Start
1983-12-01
Project End
1989-11-30
Budget Start
1988-12-01
Budget End
1989-11-30
Support Year
6
Fiscal Year
1989
Total Cost
Indirect Cost
Name
George Washington University
Department
Type
Schools of Medicine
DUNS #
City
Washington
State
DC
Country
United States
Zip Code
20052