S. Aznar et al., CONNECTIVE INTEGRATION OF HIPPOCAMPAL GRAFTS IN EXCITOTOXIC HIPPOCAMPAL-LESIONS IN ADULT-RATS - AN ANTEROGRADE AXONAL TRACING STUDY, Restorative neurology and neuroscience, 10(1), 1996, pp. 13-24
Exchange of nerve connections between developing neural grafts and adu
lt recipient brains is enhanced for grafts placed in excitotoxic lesio
ns, which spare recipient brain afferent axons in otherwise neuron-dep
leted lesion areas. In previous studies of hippocampal grafts placed i
n such lesions, we have used anterograde axonal degeneration, histoche
mical Timm staining and acetylcholinesterase to demonstrate host-graft
interconnectivity. In this study, we have now used three anterograde
axonal tracers, Phaseoulus vulgaris-leukoaglutinin (PHA-L), biocytin a
nd biotinylated dextran amine (BDA), which allow individual fibers to
be traced. Adult male rats with 1-week-old axon-sparing ibotenic acid
lesions of the dorsal CA3 region or fascia dentata were grafted into t
he respective lesions with suspensions of fetal (E18-19) CA3 cells or
a block of neonatal fascia dentata tissue. One to twelve months later,
recipients were injected with Phaseoulus vulgaris-leukoaglutinin or b
iocytin in the hippocampus contralateral to the graft to trace the pos
sible ingrowth and distribution within the transplants of host commiss
ural axons, or into the transplants with biotinylated dextran amine in
order to trace outgrowing graft fibers. In rats with succesfull host
Phaseoulus vulgaris-leukoaglutinin or biocytin injections, the CA3 and
fascia dentata transplants were innervated by labelled host commissur
al fibers. In the dentate transplants, most commissural fibers project
ed as normally to the inner part of the molecular layer, with fewer ab
errant fibers extending more superficially into the molecular layer. F
ollowing injections into the fascia dentata and CA3 grafts of biotinyl
ated dextran amine, labelled graft fibers were traced into the ipsilat
eral host dentate hilus, CA3 and CAI. From some CA3 containing grafts,
a few labelled fibers were also observed passing through the host fim
bria-fornix to the lateral septum on the grafted side. A few fibers we
re projected as far as to the most septal levels of the contralateral
CA1.