Early axonal regeneration: repression by Schwann cells and a protease?
We have proposed that mature Schwann cells and an extracellular protease repress the sprouting response of axons. To test this hypothesis, we destroyed all cells by freezing a short span of the rat sciatic nerve or inhibited proteases with subperineurial injections of aprotinin, and a crush was made to induce the sprouting response. In unconditioned or in vehicle-injected nerves, axons began to elongate at a constant rate after a delay of about 1 day. The freezing of the nerve distal to the crush obliterated the delay, but the rate of elongation did not change. A similar pattern was observed when the nerve segment was conditioned with aprotinin for 2 days prior to the crush. These effects were abolished when a short untreated segment was left between crush and conditioned region of the nerve. The electron microscopy of the nerve and the immunolocalization of the growth-associated protein (GAP-43) were consistent with the enhanced regrowth observed in conditioned nerves. Our findings support the notion that Schwann cells repress the onset of regeneration and that a local protease is involved.
Tapia
M
M
Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica, Santiago, Chile.
Inestrosa
N C
NC
Alvarez
J
J
D000818:Animals; D007611:Aprotinin / Q000494:pharmacology; D001369:Axons / Q000502:physiology*; D005615:Freezing; D009409:Nerve Crush; D009416:Nerve Regeneration; D059348:Peripheral Nerve Injuries; D010525:Peripheral Nerves / Q000502:physiology*; D011480:Protease Inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000502:physiology*; D012584:Sciatic Nerve / Q000293:injuries / Q000502:physiology; D013979:Tibial Nerve / Q000293:injuries / Q000502:physiology
D011480:Protease Inhibitors; D007611:Aprotinin