Cerebrovascular reactivity and cognitive function are impaired following chronic high-thoracic spinal cord injury
1Chornenka K, 1Jia M, 2Phillips A, 3Wang S, 1Yung A, 1Zheng M, 4Leong S, 1Kozlowski P, 3Fan F, 3Roman R, 1Krassioukov A
1International Collaboration on Repair Discoveries (ICORD), Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada; 2Physiology and Pharmacology, Cumming School of Medicine, Libin Cardiovascular Institute, Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada; 3Department of Pharmacology & Toxicology, The University of Mississippi Medical Center, Jackson, MS, USA; 4University of British Columbia, Vancouver, BC, Canada
Objective: Individuals with spinal cord injury (SCI) have compromised cerebrovascular function and a 3 to 4-fold increased risk of stroke. We have previously shown that cerebrovascular health deteriorates rapidly after experimental high-thoracic SCI, occurring in as little as 6 weeks (analogous to 2.5 human years). These changes included decreased cerebrovascular reactivity and the middle cerebral artery (MCA) suffers from inward remodeling and profibrosis. As the population of those with SCI lives longer after injury, we do not understand their trajectory of cerebrovascular decline post-injury. This study examined cerebrovascular health 14 weeks post SCI.
Design/Methods: 15 Wistar rats with intact spinal cord (control group) and 15 rats with complete T3 spinal cord transection (T3-SCI) were examined. Three months after surgery, cognitive function of all animals was evaluated with novel object recognition test. Magnetic resonance imaging (MRI) was performed to measure baseline global and regional cerebral blood flow. Animals were then sacrificed for functional and structural assessments of MCAs using ex vivo pressure myography.
Results: Short-term and spatial memory was impaired following SCI, supported by SCI animals’ impaired performance (23% less in D-index) during novel object recognition test (p=0.023). Furthermore, chronic SCI results in a 32% reduction of resting brain blood flow (p=0.028), especially in memory-associated brain regions such as the hippocampus (32%, p=0.0402). Moreover, vasodilation and vasoconstriction induced by carbachol (51%, p=0.004) and 5-HT (50%, p=0.05) respectively is significantly reduced in MCA after 3-month SCI. This indicates impaired endothelial function and construction.
Conclusion: This study provides evidence that chronic SCI leads to vascular-cognitive impairment, and provides preclinical evidence for the observed impairment of cerebrovascular regulation in humans with SCI.
Support: Heart and Stroke Foundation of Canada, Canadian Institute for Health Research, Craig H. Neilson Foundation (AVK, Principle Investigator); Heart and Stroke Foundation of Canada and Michael Smith Foundation for Health Research, and Craig H. Neilson Foundation (AAP, Post-doctoral Research Fellowships); University of British Columbia Faculty of Medicine (KC, Summer Student Research Program Award)
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