Fetal neural transplants into an area of neurodegeneration in the spinal cord of the adult rat

Abstract

Lesioning the spinal cord with an excitotoxic agent provides a model of neuronal degeneration while sparing afferent axons. The present study has been undertaken to determine whether homotypic fetal neurons transplanted as a cell suspension were able to rebuild a neural circuitry in the neuron-depleted adult cord. Fetal spinal cords, taken from rat embryos (gestational day E12–13), were transplanted as cell suspensions into an area of the lumbar cord previously depleted of neurons using kainic acid. The excitotoxic lesion extended over ventral and intermediate horns, implying the death of all motoneurons with consequent paralysis and muscular atrophy of corresponding hindlimb. During the first month after injection, the damaged cord was characterized by proliferation and recruitment of various glial cell and Schwann cell populations. First to appear were activated microglia/macrophages and next reactive astrocytes which entered the lesion from its borders with the intact tissue. Schwann cells also ensheathed central axons. Differential sensitivity of various afferents to loss of postsynaptic target neurons was observed: rubrospinal and corticospinal afferents decreased in density while no conspicuous changes were observed for immunostained CGRP-containing or monoaminergic fibers. Two to fourteen months after surgery, transplants occupied most of the neuron-depleted area. The grafts did not display a laminar organization. Monoaminergic afferents grew for a long distance and formed a network within transplants. Similarly, primary sensory CGRP-immunoreactive fibers entering in the dorsal roots penetrated deeply into transplants. In contrast, cortico- and rubrospinal afferents entered only the most peripheral portion of transplants. Our results indicate that fetal spinal neurons can be successfully transplanted into the adult neuron-depleted spinal cord. Host-to-graft connections can be formed, although their spatial extent in the transplants may depend upon features of the afferent fiber systems.