Biomaterial Database

[Stimulation of Schwann cell growth and axon regeneration of peripheral nerves by the immunosuppressive drug FK 506]. 1999

H Fansa, and G Keilhoff, and T Horn, and S Altmann, and G Wolf, and W Schneider

Klinik für Plastische, Wiederherstellungs- und Handchirurgie, Medizinische Fakultät der Otto-von-Guericke-Universität in Magdeburg.

BACKGROUND Nerve allografts are highly antigenic and, thus, require the continuous use of immunosuppressive drugs. The immunosuppressant Cyclosporine A was used in most studies. More recently, the immunosuppressive effect of FK 506 on peripheral nerve allografts and xenografts has been studied, and the drug has been found to prevent rejection successfully. However, neurotoxic complications have been noted in the central and peripheral nervous system although an increased rate of axonal regeneration has also been shown. METHODS Schwann cells were cultured from the sciatic nerve of the rat. The effect of 100 microM FK 506 administered daily on these cultures was assessed over a period of seven days and compared to an untreated control group of cultures. To visualize a direct effect of FK 506 on Schwann cells, the changes in intracellular calcium were recorded using fluorescence imaging of primary rat Schwann cell cultures loaded with Fluo-3. Regeneration of autologous nerve grafts was assessed in a rat model clinically and morphometrically after daily administration of 0.6 mg FK 506/kg body weight. RESULTS FK 506 increases the number of Schwann cells in culture significantly compared to the control group, while the fibrocyte population is decreased. FK 506 caused a transient increase of intracellular calcium levels of cultured cells. A significantly higher axon count was observed in the FK 506-treated grafts after two weeks of regeneration compared with controls. Additionally, less myelin debris was evident in the FK 506 treated group after two weeks compared with the control group. Good regeneration was noted in all grafts after six weeks of regeneration. CONCLUSIONS The increased axon counts and decreased myelin debris in the FK 506 grafts after two weeks indicate an accelerated Wallerian degeneration and increased axon sprouting into the graft initially. FK 506 promotes axonal regeneration through binding to FKBP-12, thus activating GAP-43 (growth associated protein) and the TGF beta 1-pathway (transforming growth factor). In addition, the increase of the intracellular calcium may induce Schwann cell proliferation via Calmodulin which in turn promotes axonal regeneration.

UI	MeSH Term	Description	Entries
D007166	Immunosuppressive Agents	Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-CELLS or by inhibiting the activation of HELPER CELLS. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of INTERLEUKINS and other CYTOKINES are emerging.	Immunosuppressant,Immunosuppressive Agent,Immunosuppressants,Agent, Immunosuppressive,Agents, Immunosuppressive
D008856	Microscopy, Fluorescence	Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.	Fluorescence Microscopy,Immunofluorescence Microscopy,Microscopy, Immunofluorescence,Fluorescence Microscopies,Immunofluorescence Microscopies,Microscopies, Fluorescence,Microscopies, Immunofluorescence
D009416	Nerve Regeneration	Renewal or physiological repair of damaged nerve tissue.	Nerve Tissue Regeneration,Nervous Tissue Regeneration,Neural Tissue Regeneration,Nerve Tissue Regenerations,Nervous Tissue Regenerations,Neural Tissue Regenerations,Regeneration, Nerve,Regeneration, Nerve Tissue,Regeneration, Nervous Tissue,Regeneration, Neural Tissue,Tissue Regeneration, Nerve,Tissue Regeneration, Nervous,Tissue Regeneration, Neural
D010525	Peripheral Nerves	The nerves outside of the brain and spinal cord, including the autonomic, cranial, and spinal nerves. Peripheral nerves contain non-neuronal cells and connective tissue as well as axons. The connective tissue layers include, from the outside to the inside, the epineurium, the perineurium, and the endoneurium.	Endoneurium,Epineurium,Perineurium,Endoneuriums,Epineuriums,Nerve, Peripheral,Nerves, Peripheral,Perineuriums,Peripheral Nerve
D002118	Calcium	A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.	Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D002478	Cells, Cultured	Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.	Cultured Cells,Cell, Cultured,Cultured Cell
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001369	Axons	Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body.	Axon
D012583	Schwann Cells	Neuroglial cells of the peripheral nervous system which form the insulating myelin sheaths of peripheral axons.	Schwann Cell,Cell, Schwann,Cells, Schwann
D012584	Sciatic Nerve	A nerve which originates in the lumbar and sacral spinal cord (L4 to S3) and supplies motor and sensory innervation to the lower extremity. The sciatic nerve, which is the main continuation of the sacral plexus, is the largest nerve in the body. It has two major branches, the TIBIAL NERVE and the PERONEAL NERVE.	Nerve, Sciatic,Nerves, Sciatic,Sciatic Nerves