Combination treatment with cilostazol and isosorbide mononitrate attenuates microemboli-mediated vascular cognitive impairment and improves imaging and plasma biomarkers in diabetic rats.

Autor: Li W; Ralph H. Johnson VA Medical Center, Charleston, SC, United States of America; Department of Pathology & Laboratory Medicine, Medical University of South Carolina, Charleston, SC, United States of America. Electronic address: liwe@musc.edu., Li AA; Ralph H. Johnson VA Medical Center, Charleston, SC, United States of America., Nie X; Department of Neuroscience, Medical University of South Carolina, Charleston, SC, United States of America; Center for Biomedical Imaging, Medical University of South Carolina, Charleston, SC, United States of America., Voltin J; Department of Neuroscience, Medical University of South Carolina, Charleston, SC, United States of America; Center for Biomedical Imaging, Medical University of South Carolina, Charleston, SC, United States of America., He L; Ralph H. Johnson VA Medical Center, Charleston, SC, United States of America; Department of Pathology & Laboratory Medicine, Medical University of South Carolina, Charleston, SC, United States of America., Karakaya E; Ralph H. Johnson VA Medical Center, Charleston, SC, United States of America; Department of Pathology & Laboratory Medicine, Medical University of South Carolina, Charleston, SC, United States of America., Edwards J; Ralph H. Johnson VA Medical Center, Charleston, SC, United States of America; Department of Pathology & Laboratory Medicine, Medical University of South Carolina, Charleston, SC, United States of America., Jamil S; Ralph H. Johnson VA Medical Center, Charleston, SC, United States of America; Department of Pathology & Laboratory Medicine, Medical University of South Carolina, Charleston, SC, United States of America., Abdelsaid K; Ralph H. Johnson VA Medical Center, Charleston, SC, United States of America; Department of Pathology & Laboratory Medicine, Medical University of South Carolina, Charleston, SC, United States of America., Falangola MF; Department of Neuroscience, Medical University of South Carolina, Charleston, SC, United States of America; Center for Biomedical Imaging, Medical University of South Carolina, Charleston, SC, United States of America., Ergul A; Ralph H. Johnson VA Medical Center, Charleston, SC, United States of America; Department of Pathology & Laboratory Medicine, Medical University of South Carolina, Charleston, SC, United States of America.
Jazyk: angličtina
Zdroj: Experimental neurology [Exp Neurol] 2025 Jan; Vol. 383, pp. 115030. Date of Electronic Publication: 2024 Oct 25.
DOI: 10.1016/j.expneurol.2024.115030
Abstrakt: Diabetes is a major risk factor for all types of dementia. The underlying reasons are not fully understood, and preventive therapeutic strategies are lacking. Previously we have shown that diabetic but not control rats developed a progressive cognitive decline in a microemboli (ME) model of vascular contributions to cognitive impairment & dementia (VCID). Given the cerebrovascular dysfunction is a mutual pathological change between diabetes and VCID, we hypothesized that the cognitive impairment in this ME model can be prevented by improving the endothelial function in diabetes. Our treatment paradigm was based on the LACI-2 Trial which assessed the efficacy of isosorbide mononitrate (ISMN) and cilostazol (Cil) treatments in small vessel disease progression. Control and diabetic rats were treated with ISMN/Cil or vehicle for 4 weeks, then injected with cholesterol crystal ME and the behavioral outcomes were monitored. Brain microstructure integrity was assessed by diffusion MRI. Plasma biomarkers were assessed using angiogenesis, neurology and amyloid β 42/40 panels recommended by the MarkVCID consortium. Behavioral deficits and the loss of tissue integrity previously observed in untreated diabetic rats were not noted in the treated animals in this study. Treatment improved tissue perfusion but there were no differences in plasma biomarkers. These results suggest that restoration of endothelial function with ISMN/Cil before ME injection prevented the possible deleterious effects of ME in diabetic rats by improving the endothelial integrity and it is a practical preventive and therapeutic strategy for VCID.
Competing Interests: Declaration of competing interest Weiguo Li reports financial support was provided by Diabetic Complications Research Consortium. Adviye Ergul reports financial support was provided by US Department of Veterans Affairs. Adviye Ergul reports financial support was provided by National Institutes of Health. Maria Fatima Falangola reports financial support was provided by National Institutes of Health. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024. Published by Elsevier Inc.)
Databáze: MEDLINE
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