Nerve regeneration across an extended gap: a neurobiological view of nerve repair and the possible involvement of neuronotrophic factors.

We have compared the anatomic and functional regeneration of a transected sciatic nerve following regrowth from its proximal stump through either preformed empty mesothelial chambers or autologous nerve grafts bridging a 10 mm gap. Within the mesothelial chambers an organized multifascicular nerve trunk forms between the proximal and distal stumps. After 3 months, distal segment cross sections from the mesothelial chamber and nerve graft groups did not differ with respect to axonal density or distribution of axonal diameters. Mean conduction velocities across the gaps were also similar, although the nerve graft group had a wider distribution of velocities. Little or no regeneration was evident when the gap between the nerve stumps was left empty. These results suggest that if the regrowing proximal stump is in an appropriate environment, it can form a well organized and oriented nerve trunk. In the mesothelial chambers, the regenerating nerve is surrounded by a loose cellular stroma and a small amount of interstitial fluid, which was found to contain trophic activity for cultured rodent sensory neurons. Such factors may also support nerve regeneration in vivo.

[1]  R. Adler,et al.  Neurite‐Promoting Factor in Conditioned Medium from RN22 Schwannoma Cultures: Bioassay, Fractionation, and Properties , 1982, Journal of neurochemistry.

[2]  M. Manthorpe,et al.  Schwann Cells: An in Vitro Perspective , 1982 .

[3]  Y. Goto [Experimental study of nerve autografting by funicular sxuture]. , 1967, Nihon geka hokan. Archiv fur japanische Chirurgie.

[4]  A. Berger,et al.  The Interfascicular Nerve-grafting of the Median and Ulnar Nerves , 1972 .

[5]  R. Levi‐montalcini The nerve growth factor: its mode of action on sensory and sympathetic nerve cells. , 1966, Harvey lectures.

[6]  D. Purves,et al.  Effect of nerve growth factor on synaptic depression after axotomy , 1976, Nature.

[7]  S. Varon Nerve growth factor and its mode of action , 1975, Experimental Neurology.

[8]  M. Manthorpe,et al.  Spinal cord neuronotrophic factors (SCNTFs): I. Bioassay of schwannoma and other conditioned media. , 1982, Brain research.

[9]  A. Scheibel,et al.  Degeneration and regeneration of the nervous system , 1960 .

[10]  G. Lundborg,et al.  Regeneration of peripheral nerve through a preformed tissue space. Preliminary observations on the reorganization of regenerating nerve fibres and perineurium , 1979, Brain Research.

[11]  R. Adler,et al.  Trophic and Specifying Factors Directed to Neuronal Cells , 1981 .

[12]  G. Lundborg,et al.  Reorganization and orientation of regenerating nerve fibres, perineurium, and epineurium in preformed mesothelial tubes – an experimental study on the sciatic nerve of rats , 1981, Journal of neuroscience research.

[13]  W. Rodkey,et al.  Peripheral nerve injuries: studies in higher nonhuman primates. , 1980, The Journal of hand surgery.

[14]  S. Skaper,et al.  Trophic activities for dorsal root and sympathetic ganglionic neurons in media conditioned by Schwann and other peripheral cells. , 1981, Brain research.

[15]  Bora Fw Peripheral nerve repair in cats. The fascicular stitch. , 1967 .

[16]  B. Grafstein The nerve cell body response to axotomy , 1975, Experimental Neurology.

[17]  R. W. Hakstian Funicular orientation by direct stimulation. An aid to peripheral nerve repair. , 1968, The Journal of bone and joint surgery. American volume.

[18]  R. Adler,et al.  Nerve growth factors and control of nerve growth. , 1980, Current topics in developmental biology.

[19]  G. Lundborg,et al.  Nerve regeneration model and trophic factors in vivo , 1982, Brain Research.

[20]  S. Skaper,et al.  Neuronotrophic factors and their antibodies: In vitro microassays for titration and screening , 1981, Brain Research.

[21]  J. J. Niebauer,et al.  Epineurial and perineurial fascicular nerve repairs: a critical comparison. , 1976, The Journal of hand surgery.

[22]  H. Millesi Microsurgery of Peripheral Nerves , 1973, World journal of surgery.

[23]  S. Skaper,et al.  Polyornithine-attached neurite-promoting factors (PNPFs). Culture sources and responsive neurons , 1981, Brain Research.