Transplants of immature astrocytes promote axonal regeneration in the adult rat brain

Abstract

To study beneficial effects of immature astrocytes on axonal regeneration in the injured adult mammalian brain, we have stereotactically implanted cultured astrocytes from embryonic (E 14-16) rat cerebral cortex into the lesion site following transection of the postcommissural fornix. The spatio-temporal pattern of axonal degeneration and regrowth in the proximal fornix stump was investigated using wheat germ agglutinin-horseradish peroxidase tracing techniques and quantitative analysis of myelinated axon profiles. Transection of the postcommissural fornix tract caused disintegration of the axons in the distal stump as well as rapid and pronounced retrograde axonal degeneration up to 800-1,200 microns proximal to the lesion site. While a small bundle of subicular fibers spontaneously extended to the lesion site within 4 weeks after injury, axonal regeneration was markedly stimulated in those animals that had received an astroglial implant. Following the former pathway, regenerating axons sprouted towards the implant but did not penetrate the graft. Instead, the axons elongated over the surface of the transplant, avoiding growth into the surrounding neuropil or into the distal fornix segment. In grafted animals we further observed a substantial increase in the number of myelinated axons of approximately 31.5% (at the level of 800 microns) and approximately 40% (at the 400 microns level) compared with the injured tract lacking a transplant. Our results indicate the capacity of juvenile astrocytes to stimulate axonal regeneration after injury of the post-commissural fornix tract in the adult rat brain. We further demonstrate myelination of the regenerated axons.