title: Tracking Epidermal Nerve Fiber Changes in Asian Macaques: Tools and Techniques for Quantitative Assessment.
abstract: Quantitative assessment of epidermal nerve fibers (ENFs) has become a widely used clinical tool for the diagnosis of small fiber neuropathies such as diabetic neuropathy and human immunodeficiency virus-associated sensory neuropathy (HIV-SN). To model and investigate the pathogenesis of HIV-SN using simian immunodeficiency virus (SIV)-infected Asian macaques, we adapted the skin biopsy and immunostaining techniques currently employed in human patients and then developed two unbiased image analysis techniques for quantifying ENF in macaque footpad skin. This report provides detailed descriptions of these tools and techniques for ENF assessment in macaques and outlines important experimental considerations that we have identified in the course of our long-term studies. Although initially developed for studies of HIV-SN in the SIV-infected macaque model, these methods could be readily translated to a range of studies involving peripheral nerve degeneration and neurotoxicity in nonhuman primates as well as preclinical investigations of agents aimed at neuroprotection and regeneration.
authors.affiliation: Department of Molecular and Comparative Pathobiology, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Mangus
authors.affiliation: Department of Molecular and Comparative Pathobiology, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Jamie L
authors.initials: JL
authors.lastname: Dorsey
authors.affiliation: Department of Molecular and Comparative Pathobiology, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Weinberg
authors.affiliation: Department of Neurology, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Gigi J
authors.initials: GJ
authors.lastname: Ebenezer
authors.affiliation: Department of Neurology, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA Current Affiliation: Department of Neurology, School of Medicine, University of Utah, Salt Lake City, Utah, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Hauer
authors.affiliation: Department of Molecular and Comparative Pathobiology, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA Current Affiliation: Covance Pharmaceutical Research and Development (Shanghai) Co. Ltd., Shanghai, China.
authors.forename: Victoria A
authors.initials: VA
authors.lastname: Laast
authors.affiliation: Department of Molecular and Comparative Pathobiology, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA Department of Neurology, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA Department of Pathology, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA jmankows@jhmi.edu.
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Mankowski
mesh_terms: D000818:Animals; D001706:Biopsy; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D008251:Macaca; D009410:Nerve Degeneration / Q000473:pathology* / Q000821:virology; D009412:Nerve Fibers / Q000473:pathology*; D010523:Peripheral Nervous System Diseases / Q000473:pathology* / Q000821:virology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000150:complications; D012867:Skin / Q000294:innervation / Q000473:pathology*
keywords: PGP9.5; epidermal nerve fibers; image analysis; nervous system; nonhuman primate; peripheral neuropathy; stereology