Bindemann, Neil William; (1993) The involvement of neuropeptides in nerve regeneration. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The studies presented in this thesis are concerned with the role of peptides in regeneration of the peripheral nervous system of the adult rat, and the presence of macrophages expressing different antigenic markers in the peripheral nervous system. The major section examines the time course of accumulation of two neuropeptides, calcitonin gene-related peptide (CGRP) and vasoactive intestinal peptide (VIP), as well as the lymphokine, gamma interferon (IFNy), following lesion to the sciatic nerve. Using radioimmunoassay, elevated levels of CGRP and VIP-like immunoreactivity expressed in the sciatic nerve after injury are quantified. The time course for IFNy accumulation is documented by immunohistochemistry. Data are also presented demonstrating that addition of synthetic human CGRP causes an accumulation of cyclic adenosine monophosphate (cyclic AMP) within macrophages isolated from the sciatic nerve, peritoneum and spleen. However, additional experiments demonstrate that the ability of CGRP to alter such cyclic AMP levels is influenced by the state of macrophage activation. This raises the possibility that CGRP is important for regulating the response of macrophages which infiltrate injured sciatic nerve. In the second section of the thesis, the distribution of macrophage subpopulations/phenotypes in normal versus lesioned sciatic nerve are described. A series of monoclonal antibodies to macrophage markers including, ED1,2,3, Leukocyte Common Antigen (LCA) and OX42 demonstrate how numbers and distribution of macrophage phenotypes alters in response to peripheral nerve injury.

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