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J Physiol. 2016 Mar 15;594(6):1677-88. doi: 10.1113/JP270925. Epub 2016 Jan 18.

Rigid and remodelled: cerebrovascular structure and function after experimental high-thoracic spinal cord transection.

Author information

1
International Collaboration on Repair Discoveries, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
2
Experimental Medicine Program, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
3
Centre for Heart, Lung, and Vascular Health, Faculty of Health and Social Development, University of British Columbia, Vancouver, Canada.
4
Pharmacology, Michigan State University, East Lansing, MI, USA.
5
Deptartment of Pharmacology and Therapeutic, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
6
GF Strong Rehabilitation Center, Vancouver Coastal Health, Vancouver, Canada.
7
Division of Physical Medicine and Rehabilitation, Department of Medicine, University of British Columbia, Vancouver, Canada.

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.

PMID:
26634420
PMCID:
PMC4799971
DOI:
10.1113/JP270925
[Indexed for MEDLINE]
Free PMC Article

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