TY - JOUR
T1 - Vascular-Cognitive Impairment following High-Thoracic Spinal Cord Injury Is Associated with Structural and Functional Maladaptations in Cerebrovasculature
AU - Sachdeva, Rahul
AU - Jia, Mengyao
AU - Wang, Shaoxun
AU - Yung, Andrew
AU - Zheng, Mei Mu Zi
AU - Lee, Amanda H.X.
AU - Monga, Aaron
AU - Leong, Sarah
AU - Kozlowski, Piotr
AU - Fan, Fan
AU - Roman, Richard J.
AU - Phillips, Aaron A.
AU - Krassioukov, Andrei V.
N1 - Funding Information:
The present study was supported by funds from the Heart and Stroke Foundation (G-16-00012571) and Canadian Institutes of Health Research (389694). Dr. Sachdeva is supported by Postdoctoral Fellowships from the Craig H. Neilsen Foundation (455064), Canadian Institutes of Health Research (415366), Michael Smith Foundation for Health Research (18408) and University of British Columbia (Bluma Tischler Postdoctoral Fellowship). The Phillips Lab is supported by the Wings for Life Foundation (Project Grant 202), Compute Canada (Resources for Research Groups nnu-172), Natural Sciences and Engineering Research Council (Canada; Discovery Grant RGPIN/03771-2018), the Canadian Institutes of Health Research (Project Grant 159573), Alberta Innovates Health Solutions, Campus Alberta Neuroscience, the Libin Cardiovascular Institute of Alberta, the Hotchkiss Brain Institute, and the Rick Hansen Institute. Dr. Fan and Roman Labs were supported by grants AG050049 (F.F.), AG057842 (F.F.) and HL138685 (R.J.R.) from the National Institutes of Health.
Publisher Copyright:
© Copyright 2020, Mary Ann Liebert, Inc., publishers 2020.
PY - 2020/9/15
Y1 - 2020/9/15
N2 - Individuals living with chronic spinal cord injury (SCI) often exhibit impairments in cognitive function, which impede their rehabilitation and transition into the community. Although a number of clinical studies have demonstrated the impact of impaired cardiovascular control on cognitive impairment, the mechanistic understanding of this deleterious relationship is still lacking. The present study investigates whether chronic disruption of cardiovascular control following experimental SCI results in cerebrovascular decline and vascular cognitive impairment. Fourteen weeks following a high thoracic SCI (at the third thoracic segment), rats were subjected to a battery of in vivo and in vitro physiological assessments, cognitive-behavioral tests, and immunohistochemical approaches to investigate changes in cerebrovascular structure and function in the middle cerebral artery (MCA). We show that in the MCA of rats with SCI, there is a 55% (SCI vs. control: 13.4 ± 1.9% vs. 29.63 ± 2.8%, respectively) reduction in the maximal vasodilator response to carbachol, which is associated with reduced expression of endothelial marker cluster of differentiation 31 (CD31) and transient receptor potential cation channel 4 (TRPV 4) channels. Compared with controls, MCAs in rats with SCI were found to have 50% (SCI vs. control: 1.5 ± 0.2 vs. 1 ± 0.1 a.u., respectively) more collagen 1 in the media of vascular wall and 37% (SCI vs. control: 30.5 ± 2.9% vs. 42.0 ± 4.0%, respectively) less distensibility at physiological intraluminal pressure. Further, the cerebral blood flow (CBF) in the hippocampus was reduced by 32% in the SCI group (SCI vs. control: 44.3 ± 4.5 mL/100 g/min vs. 65.0 ± 7.2 mL/100 g/min, respectively) in association with impairment of short-term memory based on a novel object recognition test. There were no changes in the sympathetic innervation of the vasculature and passive structure in the SCI group. Chronic experimental SCI is associated with structural alterations and endothelial dysfunction in cerebral arteries that likely contribute to significantly reduced CBF and vascular cognitive impairment.
AB - Individuals living with chronic spinal cord injury (SCI) often exhibit impairments in cognitive function, which impede their rehabilitation and transition into the community. Although a number of clinical studies have demonstrated the impact of impaired cardiovascular control on cognitive impairment, the mechanistic understanding of this deleterious relationship is still lacking. The present study investigates whether chronic disruption of cardiovascular control following experimental SCI results in cerebrovascular decline and vascular cognitive impairment. Fourteen weeks following a high thoracic SCI (at the third thoracic segment), rats were subjected to a battery of in vivo and in vitro physiological assessments, cognitive-behavioral tests, and immunohistochemical approaches to investigate changes in cerebrovascular structure and function in the middle cerebral artery (MCA). We show that in the MCA of rats with SCI, there is a 55% (SCI vs. control: 13.4 ± 1.9% vs. 29.63 ± 2.8%, respectively) reduction in the maximal vasodilator response to carbachol, which is associated with reduced expression of endothelial marker cluster of differentiation 31 (CD31) and transient receptor potential cation channel 4 (TRPV 4) channels. Compared with controls, MCAs in rats with SCI were found to have 50% (SCI vs. control: 1.5 ± 0.2 vs. 1 ± 0.1 a.u., respectively) more collagen 1 in the media of vascular wall and 37% (SCI vs. control: 30.5 ± 2.9% vs. 42.0 ± 4.0%, respectively) less distensibility at physiological intraluminal pressure. Further, the cerebral blood flow (CBF) in the hippocampus was reduced by 32% in the SCI group (SCI vs. control: 44.3 ± 4.5 mL/100 g/min vs. 65.0 ± 7.2 mL/100 g/min, respectively) in association with impairment of short-term memory based on a novel object recognition test. There were no changes in the sympathetic innervation of the vasculature and passive structure in the SCI group. Chronic experimental SCI is associated with structural alterations and endothelial dysfunction in cerebral arteries that likely contribute to significantly reduced CBF and vascular cognitive impairment.
KW - cerebrovascular deficit
KW - cognitive impairment
KW - endothelial dysfunction
KW - spinal cord injury
KW - vascular fibrosis
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U2 - 10.1089/neu.2019.6913
DO - 10.1089/neu.2019.6913
M3 - Article
C2 - 32394805
AN - SCOPUS:85090910519
SN - 0897-7151
VL - 37
SP - 1963
EP - 1970
JO - Central Nervous System Trauma
JF - Central Nervous System Trauma
IS - 18
ER -