Abstract
Investiture of new microvessels within an injured peripheral nerve trunk may determine the success that the local environment has in promoting axonal sprouting and regeneration. We therefore examined microvessel investment of 24 h–14 d proximal nerve stump preparations in rat sciatic nerves. The stumps, later destined to form neuromas, were created by sciatic nerve transection with resection of distal branches to prevent distal reinnervation. Microvessels were studied in the proximal stump in semithin whole mount sections of nerve and by analysis of India ink perfused microvessel profiles. Quantitative image analysis was made of the luminal profiles of vessels perfused with India ink from unfixed sections of the stumps, contralateral uninjured nerves and sham-exposed but uninjured nerves. Evidence of angiogenesis was observed in stumps 7 d after transection, indicated by a rise in the total numbers of perfused microvessels and in the numbers of 2–6 μm diameter perfused microvessels. There was a shift in the histogram of the percentage of perfused microvessels towards the 2–4 μm range and a reduction in the mean microvessel luminal area in the stumps. By 14 d, new microvessels were larger, indicated by an increase in total luminal area. New microvessels were prominent in the epineurial connective tissue or between layers of perineurial cells of former fascicles. Microvessels probably share a battery of trophic signals with other proliferating cellular elements in the milieu of the injured peripheral nerve trunk.
Keywords: Nerve regeneration, peripheral nerve, vasculature, microvessels
Full Text
The Full Text of this article is available as a PDF (515.4 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Aloe L. The effect of nerve growth factor and its antibody on mast cells in vivo. J Neuroimmunol. 1988 Apr;18(1):1–12. doi: 10.1016/0165-5728(88)90129-4. [DOI] [PubMed] [Google Scholar]
- Bell M. A., Weddell A. G. A morphometric study of intrafascicular vessels of mammalian sciatic nerve. Muscle Nerve. 1984 Sep;7(7):524–534. doi: 10.1002/mus.880070703. [DOI] [PubMed] [Google Scholar]
- Bray R. C., Fisher A. W., Frank C. B. Fine vascular anatomy of adult rabbit knee ligaments. J Anat. 1990 Oct;172:69–79. [PMC free article] [PubMed] [Google Scholar]
- Chalazonitis A., Kessler J. A., Twardzik D. R., Morrison R. S. Transforming growth factor alpha, but not epidermal growth factor, promotes the survival of sensory neurons in vitro. J Neurosci. 1992 Feb;12(2):583–594. doi: 10.1523/JNEUROSCI.12-02-00583.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cockerill G. W., Gamble J. R., Vadas M. A. Angiogenesis: models and modulators. Int Rev Cytol. 1995;159:113–160. doi: 10.1016/s0074-7696(08)62106-3. [DOI] [PubMed] [Google Scholar]
- Dethlefsen S. M., Matsuura N., Zetter B. R. Mast cell accumulation at sites of murine tumor implantation: implications for angiogenesis and tumor metastasis. Invasion Metastasis. 1994;14(1-6):395–408. [PubMed] [Google Scholar]
- Diamond J., Foerster A., Holmes M., Coughlin M. Sensory nerves in adult rats regenerate and restore sensory function to the skin independently of endogenous NGF. J Neurosci. 1992 Apr;12(4):1467–1476. doi: 10.1523/JNEUROSCI.12-04-01467.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Diamond J., Holmes M., Coughlin M. Endogenous NGF and nerve impulses regulate the collateral sprouting of sensory axons in the skin of the adult rat. J Neurosci. 1992 Apr;12(4):1454–1466. doi: 10.1523/JNEUROSCI.12-04-01454.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Finklestein S. P., Apostolides P. J., Caday C. G., Prosser J., Philips M. F., Klagsbrun M. Increased basic fibroblast growth factor (bFGF) immunoreactivity at the site of focal brain wounds. Brain Res. 1988 Sep 20;460(2):253–259. doi: 10.1016/0006-8993(88)90370-8. [DOI] [PubMed] [Google Scholar]
- Gruber B. L., Marchese M. J., Kew R. Angiogenic factors stimulate mast-cell migration. Blood. 1995 Oct 1;86(7):2488–2493. [PubMed] [Google Scholar]
- Kessler D. A., Langer R. S., Pless N. A., Folkman J. Mast cells and tumor angiogenesis. Int J Cancer. 1976 Nov 15;18(5):703–709. doi: 10.1002/ijc.2910180520. [DOI] [PubMed] [Google Scholar]
- Lindholm D., Heumann R., Meyer M., Thoenen H. Interleukin-1 regulates synthesis of nerve growth factor in non-neuronal cells of rat sciatic nerve. Nature. 1987 Dec 17;330(6149):658–659. doi: 10.1038/330658a0. [DOI] [PubMed] [Google Scholar]
- Marcarian H. Q., Smith R. D. A quantitative study on the vasa nervorum in the ulnar nerve of cats. Anat Rec. 1968 May;161(1):105–109. doi: 10.1002/ar.1091610111. [DOI] [PubMed] [Google Scholar]
- Meininger C. J., Zetter B. R. Mast cells and angiogenesis. Semin Cancer Biol. 1992 Apr;3(2):73–79. [PubMed] [Google Scholar]
- Morrison R. S., Kornblum H. I., Leslie F. M., Bradshaw R. A. Trophic stimulation of cultured neurons from neonatal rat brain by epidermal growth factor. Science. 1987 Oct 2;238(4823):72–75. doi: 10.1126/science.3498986. [DOI] [PubMed] [Google Scholar]
- Norrby K. Evidence of a dual role of endogenous histamine in angiogenesis. Int J Exp Pathol. 1995 Apr;76(2):87–92. [PMC free article] [PubMed] [Google Scholar]
- Norrby K., Sörbo J. Heparin enhances angiogenesis by a systemic mode of action. Int J Exp Pathol. 1992 Apr;73(2):147–155. [PMC free article] [PubMed] [Google Scholar]
- Olsson Y. Degranulation of mast cells in peripheral nerve injuries. Acta Neurol Scand. 1967;43(3):365–374. doi: 10.1111/j.1600-0404.1967.tb05739.x. [DOI] [PubMed] [Google Scholar]
- Olsson Y. Mast cells in the nervous system. Int Rev Cytol. 1968;24:27–70. doi: 10.1016/s0074-7696(08)61396-0. [DOI] [PubMed] [Google Scholar]
- Reed J. A., Albino A. P., McNutt N. S. Human cutaneous mast cells express basic fibroblast growth factor. Lab Invest. 1995 Feb;72(2):215–222. [PubMed] [Google Scholar]
- Schott R. J., Morrow L. A. Growth factors and angiogenesis. Cardiovasc Res. 1993 Jul;27(7):1155–1161. doi: 10.1093/cvr/27.7.1155. [DOI] [PubMed] [Google Scholar]
- Schweigerer L., Neufeld G., Friedman J., Abraham J. A., Fiddes J. C., Gospodarowicz D. Capillary endothelial cells express basic fibroblast growth factor, a mitogen that promotes their own growth. Nature. 1987 Jan 15;325(6101):257–259. doi: 10.1038/325257a0. [DOI] [PubMed] [Google Scholar]
- Walicke P., Cowan W. M., Ueno N., Baird A., Guillemin R. Fibroblast growth factor promotes survival of dissociated hippocampal neurons and enhances neurite extension. Proc Natl Acad Sci U S A. 1986 May;83(9):3012–3016. doi: 10.1073/pnas.83.9.3012. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zochodne D. W., Allison J. A., Ho W., Ho L. T., Hargreaves K., Sharkey K. A. Evidence for CGRP accumulation and activity in experimental neuromas. Am J Physiol. 1995 Feb;268(2 Pt 2):H584–H590. doi: 10.1152/ajpheart.1995.268.2.H584. [DOI] [PubMed] [Google Scholar]
- Zochodne D. W., Ho L. T. Endoneurial microenvironment and acute nerve crush injury in the rat sciatic nerve. Brain Res. 1990 Dec 3;535(1):43–48. doi: 10.1016/0006-8993(90)91822-x. [DOI] [PubMed] [Google Scholar]
- Zochodne D. W., Ho L. T. Hyperemia of injured peripheral nerve: sensitivity to CGRP antagonism. Brain Res. 1992 Dec 11;598(1-2):59–66. doi: 10.1016/0006-8993(92)90168-9. [DOI] [PubMed] [Google Scholar]
- Zochodne D. W., Huang Z. X., Ward K. K., Low P. A. Guanethidine-induced adrenergic sympathectomy augments endoneurial perfusion and lowers endoneurial microvascular resistance. Brain Res. 1990 Jun 11;519(1-2):112–117. doi: 10.1016/0006-8993(90)90067-l. [DOI] [PubMed] [Google Scholar]
- Zochodne D. W., Nguyen C., Sharkey K. A. Accumulation and degranulation of mast cells in experimental neuromas. Neurosci Lett. 1994 Nov 21;182(1):3–6. doi: 10.1016/0304-3940(94)90191-0. [DOI] [PubMed] [Google Scholar]