Age-dependent VEGF expression and intraneural neovascularization during regeneration of peripheral nerves.
The physiologic ability of peripheral nerves to regenerate after injury is impaired with aging. However, the mechanisms responsible for this phenomenon are still incompletely characterized. In this study, we investigated whether aging influences the intraneural angiogenic response that occurs after injury and during regeneration of peripheral nerves. We performed a crush injury of the sciatic nerve in old and senescence accelerated mice and found that the peripheral nerves of these animals are unable to locally upregulate vascular endothelial growth factor (VEGF), a prototypical angiogenic cytokine, after injury and have substantial deficits in mounting an appropriate intraneural angiogenic response during nerve regeneration. Our findings provide new evidence of possible interdependent relationships between aging, VEGF, angiogenesis, and nerve regeneration and suggest that vascular abnormalities might play a role in aging-associated neurological dysfunction, with potentially important fundamental and clinical implications.
Pola
Roberto
R
Department of Medicine (Cardiovascular Research), St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, MA, USA. rob_pola@hotmail.com
Aprahamian
Tamar R
TR
Bosch-Marcé
Marta
M
Curry
Cynthia
C
Gaetani
Eleonora
E
Flex
Andrea
A
Smith
Roy C
RC
Isner
Jeffrey M
JM
Losordo
Douglas W
DW
D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000502:physiology*; D009416:Nerve Regeneration / Q000502:physiology*; D009431:Neural Conduction / Q000502:physiology; D059348:Peripheral Nerve Injuries; D010525:Peripheral Nerves / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology; D020127:Recovery of Function / Q000502:physiology; D012584:Sciatic Nerve / Q000098:blood supply / Q000293:injuries* / Q000473:pathology / Q000503:physiopathology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D042461:Vascular Endothelial Growth Factor A