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

Key Points Spinal cord injury (SCI) is associated with a 3–4 fold increased risk of stroke, and impaired cerebral blood flow regulation, although the effect of SCI on the structure and function of the cerebral arteries is unclear. Using pressure myography to assess isolated vessels distended at physiological pressures, we provide novel evidence that experimental SCI leads to inward cerebrovascular remodelling, increased stiffness and impaired reactivity of the largest cerebral artery. Histochemical analyses revealed that a profibrotic environment within the largest cerebral artery occurs after SCI, which was characterized by greater collagen and less elastin. This may be due to increased transforming growth factor β, a well-known profibrotic signalling protein. Further analysis revealed that profibrotic alterations were not due to disruption of descending sympathetic pathways to the cerebrovasculature. Experimental SCI exerts a deleterious influence on the structure and function of cerebral arteries, which may underlie the increased risk of stroke and impaired cerebral blood flow regulation. 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.