title: Dorsal column sensory axons degenerate due to impaired microvascular perfusion after spinal cord injury in rats.
abstract: The mechanisms contributing to axon loss after spinal cord injury (SCI) are largely unknown but may involve microvascular loss as we have previously suggested. Here, we used a mild contusive injury (120 kdyn IH impactor) at T9 in rats focusing on ascending primary sensory dorsal column axons, anterogradely traced from the sciatic nerves. The injury caused a rapid and progressive loss of dorsal column microvasculature and oligodendrocytes at the injury site and penumbra and an ~70% loss of the sensory axons by 24 h. To model the microvascular loss, focal ischemia of the T9 dorsal columns was achieved via phototoxic activation of intravenously injected rose bengal. This caused an ~53% loss of sensory axons and an ~80% loss of dorsal column oligodendrocytes by 24 h. Axon loss correlated with the extent and axial length of microvessel and oligodendrocyte loss along the dorsal column. To determine if oligodendrocyte loss contributes to axon loss, the glial toxin ethidium bromide (EB; 0.3 μg/μl) was microinjected into the T9 dorsal columns, and resulted in an ~88% loss of dorsal column oligodendrocytes and an ~56% loss of sensory axons after 72 h. EB also caused an ~75% loss of microvessels. Lower concentrations of EB resulted in less axon, oligodendrocyte and microvessel loss, which were highly correlated (R(2) = 0.81). These data suggest that focal spinal cord ischemia causes both oligodendrocyte and axon degeneration, which are perhaps linked. Importantly, they highlight the need of limiting the penumbral spread of ischemia and oligodendrocyte loss after SCI in order to protect axons.
authors: Kentucky Spinal Cord Injury Research Center, University of Louisville, KY 40292, USA; Department of Neurological Surgery, University of Louisville, KY 40292, USA.
authors: Johongir M
authors: JM
authors: Muradov
authors: Eric E
authors: EE
authors: Ewan
authors: Theo
authors: T
authors: Hagg
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism / Q000473:pathology*; D005260:Female; D008833:Microcirculation / Q000502:physiology*; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D020671:Posterior Horn Cells / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000378:metabolism / Q000473:pathology*; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D013904:Thoracic Vertebrae
keywords: Axonal degeneration; Blood flow; Capillaries; Contusion; Ischemia; Oligodendrocytes; Spinal cord injury
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