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©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
Three-dimensional-arterial spin labeling perfusion correlation with diabetes-associated cognitive dysfunction and vascular endothelial growth factor in type 2 diabetes mellitus rat
Ju-Wei Shao, Jin-De Wang, Qian He, Ying Yang, Ying-Ying Zou, Wei Su, Shu-Tian Xiang, Jian-Bo Li, Jing Fang
Ju-Wei Shao, Qian He, Wei Su, Shu-Tian Xiang, Jian-Bo Li, Department of Radiology, The Second People’s Hospital of Yunnan Province, The Affiliated Hospital of Yunnan University, Kunming 650021, Yunnan Province, China
Ju-Wei Shao, College of Public Health, Kunming Medical University, Kunming 650500, Yunnan Province, China
Jin-De Wang, College of Clinical Medicine, Kunming Medical University, Kunming 650500, Yunnan Province, China
Ying Yang, Department of Endocrinology and Metabolism, The Second People’s Hospital of Yunnan Province, The Affiliated Hospital of Yunnan University, Kunming 650021, Yunnan Province, China
Ying-Ying Zou, Department of Pathology and Pathophysiology, Kunming Medical University, Kunming 650021, Yunnan Province, China
Jing Fang, Institute for Health Sciences, Kunming Medical University, Kunming 650500, Yunnan Province, China
Author contributions: Shao JW designed experiments, performed the literature review, and wrote the draft of the paper; Wang JD and Zou YY helped establish the type 2 diabetes mellitus rat models and assisted in the histopathologic procedures; Li JB scanned the rats; Su W collected the data; He Q and Xiang ST corrected the data; Yang Y also contributed to the writing and editing of the manuscript, which was critically revised and edited by Fang J; All authors approved the final version.
Supported by The Endocrine Clinical Medical Center of Yunnan Province, No. ZX20190202; the Fund of the Diabetic Innovation Team in Yunnan Province, No. 2019HC002; the Special Joint Fund from Yunnan Provincial Department of Science and Technology and Kunming Medical University, Kunming, Yunnan, China, No. 2018FE001(-267); and the SKY Image Research Fund, China, No. Z-2014-07-2003-12.
Institutional animal care and use committee statement: All animal experiments conformed to the internationally accepted principles for the care and use of laboratory animals (Kunming Medical University Institutional Review Board, Approval No. kmmu 2020410).
Conflict-of-interest statement: No potential conflicts of interest.
Data sharing statement: Technical appendix, statistical code, and data set available from the corresponding author at fangjing07@126.com. Participants gave informed consent for data sharing. No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
http://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Jing Fang, MD, Professor, Institute for Health Sciences, Kunming Medical University, No. 1168 Chunrong West Road, Yuhua Street, Chenggong District, Kunming 650031, Yunnan Province, China. fangjing07@126.com
Received: December 11, 2020
Peer-review started: December 11, 2020
First decision: January 11, 2021
Revised: January 12, 2021
Accepted: March 7, 2021
Article in press: March 7, 2021
Published online: April 15, 2021
ARTICLE HIGHLIGHTS
Research background
The mechanisms of diabetes-associated cognitive dysfunction (DACD) have not been fully elucidated to date. Some studies proved that lower cerebral blood flow (CBF) in the hippocampus was associated with poor executive function and memory in type 2 diabetes mellitus (T2DM). Increasing evidence showed that diabetes leads to abnormal vascular endothelial growth factor (VEGF) expression and CBF changes in humans and animal models. This study explored whether DACD was correlated with CBF alteration and VEGF expression in the hippocampus.
Research motivation
Our study aimed to assess the relationship among CBF alteration, VEGF expression in the hippocampus, and DACD. Our findings may help reveal the mechanisms of DACD. This study would help in the detection of DACD and guide treatment.
Research objectives
This study aimed to explore whether VEGF signaling in the hippocampus in the T2DM rat model was related to CBF (measured by three dimensional arterial spin labeling) and DACD.
Research methods
Forty specific-pathogen-free grade Sprague-Dawley male rats were randomly divided into normal control and T2DM groups. The T2DM group was kept on a high-fat diet and then streptozotocin was administered by intraperitoneal injections to induce diabetes. The Morris water maze test was conducted to explore the learning performance and spatial memory ability of experimental rats. CBF measured by three dimensional arterial spin labeling was detected in the bilateral hippocampus. Immunofluorescence of VEGF in the bilateral hippocampus was performed, and VEGF expression was quantified with quantitative real-time PCR.
Research results
Our data indicated that the spatial learning memory ability in the T2DM group significantly decreased. An obvious reduction in CBF in rats with T2DM in the bilateral hippocampal area was observed. The expression of VEGF was lower in the T2DM group than in the control group. VEGF expression positively correlated with the CBF value in the hippocampus. A significant correlation was found between CBF and the spatial learning memory ability in the T2DM group.
Research conclusions
The new theories of this study was low perfusion of the hippocampus was associated with DACD and decreased VEGF expression in the hippocampal area of rats in the T2DM group in long-term hyperglycemia. To the best of our knowledge, this was the first study to explore the relationship of DACD, VEGF expression, and CBF of the hippocampus.
Research perspectives
Decreased CBF and low VEGF levels in the hippocampus might be risk factors for DACD. CBF measured by three dimensional arterial spin labeling might serve as a noninvasive imaging biomarker for detecting cognitive impairment associated with T2DM.
