Wallerian degeneration and axonal regeneration after sciatic nerve crush are altered in ICAM-1-deficient mice.
The intercellular cell adhesion molecule-1 (ICAM-1) has been implicated in the recruitment of immune cells during inflammatory processes. Previous studies investigating its involvement in the process of Wallerian degeneration and focusing on its potential role in macrophage recruitement have come to controversial conclusions. To examine whether Wallerian degeneration is altered in the absence of ICAM-1, we have analyzed changes in the expression of axonal and Schwann cell markers following sciatic nerve crush in wildtype and ICAM-1-deficient mice. We report that the lack of ICAM-1 leads to impaired axonal degeneration and regeneration and to alterations in Schwann cell responses following sciatic nerve crush. Degradation of neurofilament protein, the collapse of axonal profiles, and the re-expression of neurofilament proteins are substantially delayed in the distal nerve segment of ICAM-1(-/-) mice. In contrast, the degradation of myelin, as determined by immunostaining for myelin protein zero, is unaltered in the mutants. Upregulation of GAP-43 and p75 neurotrophin receptor (p75(NTR)) expression, characteristic for Schwann cells dedifferentiating in response to nerve injury, is differentially altered in the mutant animals. These results indicate that ICAM-1 is essential for the normal progression of axonal degeneration and regeneration in distal segments of injured peripheral nerves.
Kirsch
Matthias
M
Institute of Anatomy and Cell Biology, University of Freiburg, 79104, Freiburg, Germany.
Campos Friz
Marianella
M
Vougioukas
Vassilios I
VI
Hofmann
Hans-Dieter
HD
D000818:Animals; D019922:GAP-43 Protein / Q000235:genetics / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009186:Myelin Sheath / Q000378:metabolism; D009416:Nerve Regeneration / Q000502:physiology*; D012584:Sciatic Nerve / Q000166:cytology / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D014855:Wallerian Degeneration / Q000473:pathology / Q000503:physiopathology*
D019922:GAP-43 Protein; D018799:Intercellular Adhesion Molecule-1