title: Reduced thrombomodulin in human peripheral nerve microvasculature.
abstract: Thrombomodulin (TM), a vascular endothelial receptor, terminates the actions of thrombin and accelerates activated protein C formation. TM is ubiquitous throughout the systemic microcirculation but is reduced in brain regions predisposed to lacunar infarction. We investigated whether TM is present within human nerve and differentially expressed according to vessel caliber and proximity to the blood-nerve barrier. Vascular endothelial TM was detected on sural nerve biopsies with immunohistochemistry. The proportion of TM-positive microvessels was expressed relative to total von Willebrand factor (vWF)-positive vessels. Although vWF was detectable in all microvessels, TM expression was absent from the perineurial vessels. TM was detected in 47% (15-80%, 95% confidence level) of larger epineurial arterioles, in 43% (30-61%) of smaller epineurial vessels, and in 30% (19-47%) of endoneurial vessels. These findings demonstrate that TM is present in human nerve microvasculature but is regionally deficient in proximity to the blood-nerve barrier, which may predispose nerve to microvascular ischemia in inflammatory/prothrombotic conditions.
authors.affiliation: Department of Neurology, University of Maryland School of Medicine, 22 South Greene Street, Baltimore, Maryland 21201-1595, USA. cmacko@grecc.umaryland.edu
authors.forename: Charlene E
authors.initials: CE
authors.lastname: Hafer-Macko
authors.forename: Frederick M
authors.initials: FM
authors.lastname: Ivey
authors.forename: Kymberly A
authors.initials: KA
authors.lastname: Gyure
authors.forename: John D
authors.initials: JD
authors.lastname: Sorkin
authors.forename: Richard F
authors.initials: RF
authors.lastname: Macko
mesh_terms: D001706:Biopsy; D006801:Humans; D008833:Microcirculation / Q000502:physiology; D010525:Peripheral Nerves / Q000378:metabolism / Q000473:pathology; D010523:Peripheral Nervous System Diseases / Q000378:metabolism* / Q000473:pathology; D013497:Sural Nerve / Q000098:blood supply* / Q000378:metabolism* / Q000473:pathology; D018180:Thrombomodulin / Q000378:metabolism*; D013927:Thrombosis / Q000378:metabolism*
chemical_list: D018180:Thrombomodulin