Initial upregulation of growth factors and inflammatory mediators during nerve regeneration in the presence of cell adhesive peptide-incorporated collagen tubes

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J Peripher Nerv Syst. 2005 Mar;10(1):17-30.

(Note: mentions NT3 & 4 - Nerve Growth Factors we have been following ~ GG)

Initial upregulation of growth factors and inflammatory mediators during nerve

regeneration in the presence of cell adhesive peptide-incorporated collagen

tubes.

Ahmed MR, Basha SH, Gopinath D, Muthusamy R, Jayakumar R.

Bio-organic and Neurochemistry Laboratory, Central Leather Research Institute,

Adyar, India.

Abstract Neurotrophic factors play an important modulatory role in axonal

sprouting during nerve regeneration involving the proliferation of hematogenous

and Schwann cells in damaged tissue. We have exposed lesioned sciatic nerves to

a collagen prosthesis with covalently bonded small cell adhesive peptides

Arg-Gly-Asp-Ser (RGDS), Lys-Arg-Asp-Ser (KRDS), and Gly-His-Lys (GHK) to study

local production of growth factors and cytokines in the regenerating tissues.

Western/enzyme-linked immunosorbent assay (ELISA) studies were performed after

10 days of regeneration, when the tubular prosthesis is filled with fibrous

matrix infiltrated by hematogenous cells and proliferating Schwann cells with

growth factors produced locally. Regeneration was also analyzed by

morphometrical methods after 30 days.

The quantification of growth factors and proteins by ELISA revealed that there

was an enhanced expression of the neurotrophic factors nerve growth factor (NGF)

and neurotrophins (NT-3 and NT-4) in the regenerating tissues. This was further

established by Western blot to qualitatively analyze the presence of the

antigens in the regenerating tissues.

Schwann cells were localized in the regenerating tissues using antibodies

against S-100 protein. Other growth factors including growth-associated protein

43 (GAP-43), apolipoprotein E (Apo E), and pro-inflammatory cytokine like

interleukin-1alpha (IL-1alpha) expression in the peptide groups were evaluated

by ELISA and confirmed by Western blotting.

Cell adhesive integrins in the proliferating cells were localized using

integrin-alphaV. The combined results suggest that the early phase of

regeneration of peripheral nerves in the presence of peptide-incorporated

collagen tubes results in the enhanced production of trophic factors by the

recruited hematogenous cells and Schwann cells, which in turn help in the

secretion of certain vital trophic and tropic factors essential for early

regeneration. Furthermore, hematogenous cells recruited within the first 10 days

of regeneration help in the production of inflammatory mediators like

interleukins that in turn stimulate Schwann cells to produce NGF for axonal

growth.

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