The macrophage in neural injury
Abstract
We have evaluated the timing, density, and cytokine production of activated macrophages accumulating in a compression injury to the rat spinal cord and a crush injury to the sciatic nerve of the same animal. We have determined the density of these cells at the actual site of mechanical damage and a 1–2 mm distant region of Wallerian degeneration, as well as their production of the pro-inflammatory cytokines TNFα, IL-1, and IL-6, at 3, 5, 10, and 21 days post-injury. Macrophage counts were made using a new computer assisted morphometric technique in which the cell counting phase does not require human interaction with the data, and is based on identification of activated macrophages using the monoclonal antibody ED 1. Cytokine bioassays were performed on plated macrophages using spectrophotometric cell growth/cell kill analytical techniques. Cytokine concentrations were normalized per macrophage DNA as well as cell density in the injured tissue. We further describe the ultrastructure of macrophages and report the finding of giant multinucleated cells, markers of chronic inflammation, as early as 5 days post-injury in the spinal cord. Our data does not support the prevailing view that macrophage accumulations are lower in number, and delayed in their appearance, in central lesions compared to peripheral ones. The initial accumulation of activated macrophages was similar in density at both the central (CNS) and peripheral nervous system (PNS) sites of damage. Subsequently, macrophage densities at all locations studied were strikingly and significantly higher (P < 0.05) in the spinal cord than the densities observed in the sciatic nerve at every time-point but one. Further, especially at early time-points, macrophages harvested from injured CNS had a much greater ability to produce cytokines than those harvested from damaged PNS, making cytokine levels substantially greater in the injured CNS. We interpret these data relative to the well known difference in functional outcome between PNS and CNS injury.
Degree
Ph.D.
Advisors
Borgens, Purdue University.
Subject Area
Neurology|Immunology|Pathology
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