Implants of Cultured Schwann Cells Support Axonal Growth in the Central Nervous System of Adult Rats

Abstract

Growing axons require an appropriate substrate on which to elongate. In the peripheral nervous system Schwann cells provide this substrate, and in the developing central nervous system (CNS) astrocytes are involved. In the adult CNS damaged axons do not normally regenerate but they can grow through peripheral nerve grafts. Also, they can grow along sheets of implanted Schwann cells or astrocytes. This study examines the ability of dissociated suspensions of Schwann cells and astrocytes to support axonal growth when implanted into the brains of adult rats. Schwann cells and astrocytes are cultured from near-term rat fetuses or newborn pups. They are transferred to polycarbonate tubes, and one end of each tube is inserted into the dorsal thalamus. The other end is secured extracranially. After 4 weeks to 6 months, the tubes are filled with tissue and are well vascularized. Evidence that Schwann cells support axonal growth comes from retrograde labeling studies in which horseradish peroxidase is applied to the extracranial ends of the tubes. In addition, immunolabeling reveals axon-like fibers inside the tubes using three neuron-specific antibodies. Finally, electron microscopy shows that these tubes contain small peripheral nerve-like structures consisting of myelinated and unmyelinated axons and a perineurial wrapping. Tubes filled with astrocytes contain less tissue than Schwann cell tubes and cells in the brain could not be retrogradely labeled by applying HRP to the extracranial ends. However, immunocytochemical studies reveal axon-like fibers extending for several millimeters into these tubes although few, if any, reach the external end.