title: Rigid and remodelled: cerebrovascular structure and function after experimental high-thoracic spinal cord transection.
abstract: High-thoracic or cervical spinal cord injury (SCI) is associated with several critical clinical conditions related to impaired cerebrovascular health, including: 300-400% increased risk of stroke, cognitive decline and diminished cerebral blood flow regulation. The purpose of this study was to examine the influence of high-thoracic (T3 spinal segment) SCI on cerebrovascular structure and function, as well as molecular markers of profibrosis. Seven weeks after complete T3 spinal cord transection (T3-SCI, n = 15) or sham injury (Sham, n = 10), rats were sacrificed for either middle cerebral artery (MCA) structure and function assessments via ex vivo pressure myography, or immunohistochemical analyses. Myogenic tone was unchanged, but over a range of transmural pressures, inward remodelling occurred after T3-SCI with a 40% reduction in distensibility (both P < 0.05), and a 33% reduction in vasoconstrictive reactivity to 5-HT trending toward significance (P = 0.09). After T3-SCI, the MCA had more collagen I (42%), collagen III (24%), transforming growth factor β (47%) and angiotensin II receptor type 2 (132%), 27% less elastin as well as concurrent increased wall thickness and reduced lumen diameter (all P < 0.05). Sympathetic innervation (tyrosine hydroxylase-positive axon density) and endothelium-dependent dilatation (carbachol) of the MCA were not different between groups. This study demonstrates profibrosis and hypertrophic inward remodelling within the largest cerebral artery after high-thoracic SCI, leading to increased stiffness and possibly impaired reactivity. These deleterious adaptations would substantially undermine the capacity for regulation of cerebral blood flow and probably underlie several cerebrovascular clinical conditions in the SCI population.
authors.affiliation: International Collaboration on Repair Discoveries, Faculty of Medicine, University of British Columbia, Vancouver, Canada.|Experimental Medicine Program, Faculty of Medicine, University of British Columbia, Vancouver, Canada.|Centre for Heart, Lung, and Vascular Health, Faculty of Health and Social Development, University of British Columbia, Vancouver, Canada.
authors.forename: A A
authors.initials: AA
authors.lastname: Phillips
authors.affiliation: Pharmacology, Michigan State University, East Lansing, MI, USA.
authors.forename: N
authors.initials: N
authors.lastname: Matin
authors.affiliation: International Collaboration on Repair Discoveries, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
authors.forename: B
authors.initials: B
authors.lastname: Frias
authors.affiliation: International Collaboration on Repair Discoveries, Faculty of Medicine, University of British Columbia, Vancouver, Canada.|Experimental Medicine Program, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
authors.forename: M M Z
authors.initials: MM
authors.lastname: Zheng
authors.affiliation: International Collaboration on Repair Discoveries, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Jia
authors.affiliation: International Collaboration on Repair Discoveries, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
authors.forename: C
authors.initials: C
authors.lastname: West
authors.affiliation: Pharmacology, Michigan State University, East Lansing, MI, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Dorrance
authors.affiliation: Deptartment of Pharmacology and Therapeutic, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
authors.forename: I
authors.initials: I
authors.lastname: Laher
authors.affiliation: International Collaboration on Repair Discoveries, Faculty of Medicine, University of British Columbia, Vancouver, Canada.|GF Strong Rehabilitation Center, Vancouver Coastal Health, Vancouver, Canada.|Division of Physical Medicine and Rehabilitation, Department of Medicine, University of British Columbia, Vancouver, Canada.
authors.forename: A V
authors.initials: AV
authors.lastname: Krassioukov
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D004549:Elastin / Q000235:genetics / Q000378:metabolism; D005355:Fibrosis; D008297:Male; D020768:Middle Cerebral Artery / Q000294:innervation / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000473:pathology / Q000503:physiopathology*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism; D014661:Vasoconstriction
chemical_list: D044139:Receptor, Angiotensin, Type 2; D016212:Transforming Growth Factor beta; D003094:Collagen; D004549:Elastin; D014446:Tyrosine 3-Monooxygenase