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Review
. 2008;110(5):351-62.
doi: 10.1016/j.acthis.2007.12.004. Epub 2008 Apr 1.

Epidermal nerve fiber quantification in the assessment of diabetic neuropathy

Affiliations
Review

Epidermal nerve fiber quantification in the assessment of diabetic neuropathy

Kristina K Beiswenger et al. Acta Histochem. 2008.

Abstract

Assessment of cutaneous innervation in skin biopsies is emerging as a valuable means of both diagnosing and staging diabetic neuropathy. Immunolabeling, using antibodies to neuronal proteins such as protein gene product 9.5, allows for the visualization and quantification of intraepidermal nerve fibers. Multiple studies have shown reductions in intraepidermal nerve fiber density in skin biopsies from patients with both type 1 and type 2 diabetes. More recent studies have focused on correlating these changes with other measures of diabetic neuropathy. A loss of epidermal innervation similar to that observed in diabetic patients has been observed in rodent models of both type 1 and type 2 diabetes and several therapeutics have been reported to prevent reductions in intraepidermal nerve fiber density in these models. This review discusses the current literature describing diabetes-induced changes in cutaneous innervation in both human and animal models of diabetic neuropathy.

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Figures

Figure 1
Figure 1
Micrographs of foot skin from a control rat (a), a streptozotocin-injected rat with diabetes for a duration of two months (b), a control mouse (c) and streptozotocin-injected mouse with diabetes for a duration of one month (d) immunolabeled for binding of an antibody against the pan-axonal marker PGP9.5. Circles identify immunoreactive profiles, the arrow denotes a Langerhans cell and the arrowheads denote subepidermal nerve plexuses. Bar, 40 μm.
Figure 2
Figure 2
Micrographs of rat skin immunolabeled for binding of antibodies against PGP9.5 (a) and Tau (b). A comparison of immunoreactive profile densities between control rat skin sections immunolabeled for binding of each antibody revealed no significant differences (c). Langerhans cells (circled) are only prominent in PGP9.5-labeled rat skin (d). Arrows denote immunoreactive profiles. Data are mean+SEM of N=9–10/group. Bar, 40μm.
Figure 3
Figure 3
A comparison of epidermal thickness between control rats and rats with STZ-induced diabetes for a duration of two months (a) and control mice and mice with STZ-induced diabetes for a duration of one month (b). The epidermis from the diabetic group is significantly thinner in both rats and mice (p<0.001 and p<0.01, respectively, unpaired t-test). Data are mean+SEM of N=8–11/group.

References

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