title: Differential cavitation, angiogenesis and wound-healing responses in injured mouse and rat spinal cords.
abstract: The vascular disruption, blood vessel loss and cavitation that occur at spinal cord injury (SCI) epicenters in mice and rats are different, but few studies have compared the acute SCI response in the two species. This is of interest since key elements of the rat SCI response are shared with humans. In this study, we investigated acute SCI responses and characterized changes in pro- and anti-angiogenic factors and matrix deposition in both species. Cavitation was absent in mouse but the area of the lesion site was 21- and 27-fold larger at 8 and 15 days post-lesion (dpl), respectively, in the rat compared to intact control. The absence of wound cavitation in the mouse was correlated with increased levels of immunoreactive pro-angiogenic, pro-matrix and pro-wound-healing factors, e.g. laminin, matrix metalloproteinase-1 (MMP-1) and vascular endothelial growth factor-A (VEGF-A) within the wound, which were 6.0-, 2.9-, and 2.8-fold, respectively, higher in the mouse compared to rats at 8 dpl. Increased axonal sparing was observed after dorsal column (DC) injury, detected by higher levels of neurofilament 200 (NF200) immunoreactivity in the dorsal column of mice compared to rats at both T7 and T9 spinal segments. Despite similar post SCI deficits in plantar heat tests at 2h after injury (1.4- and 1.6-fold lower than control mice and rats, respectively), by 7 days the magnitude of these responses were comparable to sham-treated controls in both species, while no post-SCI changes in Von Frey hair filament test response were observed in either species. We conclude that the more robust angiogenesis/wound-healing response in the mouse attenuates post-injury wound cavitation. Although the spinal cord functions that were monitored post-injury were similarly affected in both species, we suggest that the quality of the angiogenesis/wound-healing response together with the diminished lesion size seen after mouse SCI may protect against secondary axon damage and create an environment more conducive to axon sprouting/regeneration. These results suggest the potential therapeutic utility of manipulating the angiogenic response after human SCI.
authors.affiliation: Neurotrauma and Neurodegeneration Section, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham B15 2TT, UK.
authors.forename: S
authors.initials: S
authors.lastname: Surey
authors.affiliation: Neurotrauma and Neurodegeneration Section, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham B15 2TT, UK.
authors.forename: M
authors.initials: M
authors.lastname: Berry
authors.affiliation: Neurotrauma and Neurodegeneration Section, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham B15 2TT, UK.
authors.forename: A
authors.initials: A
authors.lastname: Logan
authors.affiliation: CRUK Molecular Angiogenesis Group, School of Immunity and Infection, University of Birmingham, Birmingham B15 2TT, UK.
authors.forename: R
authors.initials: R
authors.lastname: Bicknell
authors.affiliation: Neurotrauma and Neurodegeneration Section, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham B15 2TT, UK. Electronic address: z.ahmed.1@bham.ac.uk.
authors.forename: Z
authors.initials: Z
authors.lastname: Ahmed
mesh_terms: D000818:Animals; D005260:Female; D007797:Laminin / Q000378:metabolism; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D051379:Mice; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology*; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology*
chemical_list: D007797:Laminin; D042461:Vascular Endothelial Growth Factor A; D020781:Matrix Metalloproteinase 1
keywords: angiogenesis; cavitation; mouse; rat; spinal cord injury; wound healing