- Pathophysiology
- Glial and Vascular Cell Regulation of the Blood-Brain Barrier in Diabetes
-
Xiaolong Li, Yan Cai, Zuo Zhang, Jiyin Zhou
-
Diabetes Metab J. 2022;46(2):222-238. Published online March 18, 2022
-
DOI: https://doi.org/10.4093/dmj.2021.0146
-
-
8,563
View
-
363
Download
-
21
Web of Science
-
22
Crossref
-
Abstract
PDFPubReader ePub
- As a structural barrier, the blood-brain barrier (BBB) is located at the interface between the brain parenchyma and blood, and modulates communication between the brain and blood microenvironment to maintain homeostasis. The BBB is composed of endothelial cells, basement membrane, pericytes, and astrocytic end feet. BBB impairment is a distinguishing and pathogenic factor in diabetic encephalopathy. Diabetes causes leakage of the BBB through downregulation of tight junction proteins, resulting in impaired functioning of endothelial cells, pericytes, astrocytes, microglia, nerve/glial antigen 2-glia, and oligodendrocytes. However, the temporal regulation, mechanisms of molecular and signaling pathways, and consequences of BBB impairment in diabetes are not well understood. Consequently, the efficacy of therapies diabetes targeting BBB leakage still lags behind the requirements. This review summarizes the recent research on the effects of diabetes on BBB composition and the potential roles of glial and vascular cells as therapeutic targets for BBB disruption in diabetic encephalopathy.
-
Citations
Citations to this article as recorded by
- Gut microbiota and type 2 diabetes mellitus: a focus on the gut-brain axis
Yi Pan, Tong Bu, Xia Deng, Jue Jia, Guoyue Yuan Endocrine.2024; 84(1): 1. CrossRef - Long-Term Exposure of Cultured Astrocytes to High Glucose Impact on Their LPS-Induced Activation
Ayna Abdyeva, Ekaterina Kurtova, Irina Savinkova, Maksim Galkov, Liubov Gorbacheva International Journal of Molecular Sciences.2024; 25(2): 1122. CrossRef - Role of autophagy in angiogenic potential of vascular pericytes
Soheil Zamen Milani, Aysa Rezabakhsh, Mohammad Karimipour, Leila Salimi, Narges Mardi, Maryam Taghavi Narmi, Fatemeh Sadeghsoltani, Ferzane Valioglu, Reza Rahbarghazi Frontiers in Cell and Developmental Biology.2024;[Epub] CrossRef - Hyperglycaemia perturbs blood-brain barrier integrity through its effects on endothelial cell characteristics and function
Arshad Hashmat, Jingyuan Ya, Rais Kadir, Mansour Alwjwaj, Ulvi Bayraktutan Tissue Barriers.2024;[Epub] CrossRef - Endothelial dysfunction in neurodegenerative disease: Is endothelial inflammation an overlooked druggable target?
Megan Ritson, Caroline P.D. Wheeler-Jones, Helen B. Stolp Journal of Neuroimmunology.2024; 391: 578363. CrossRef - Dynamic changes in key factors of the blood-brain barrier in early diabetic mice
Zhi-yong Xu, Shu-xian Fu, Hui-chao Zhao, Yin-min Wang, Yan Liu, Jin-you Ma, Yan Yu, Jia-Le Zhang, Zhan-peng Han, Ming-xue Zheng Journal of Neuropathology & Experimental Neurology.2024; 83(9): 763. CrossRef - Di(2-ethylhexyl) phthalate exposure aggravates hypoxia/reoxygenation injury in cerebral endothelial cells by downregulating epithelial cadherin expression
Jin Hee Kim, Jae Hoon Lee, Zhengyu Nan, Ja Woo Choi, Jong Wook Song Toxicology Research.2024;[Epub] CrossRef - Advancing the understanding of diabetic encephalopathy through unravelling pathogenesis and exploring future treatment perspectives
Aarti Nagayach, Rakesh Bhaskar, Shampa Ghosh, Krishna Kumar Singh, Sung Soo Han, Jitendra Kumar Sinha Ageing Research Reviews.2024; 100: 102450. CrossRef - Hyperglycemia in a NOD Mice Model of Type-I Diabetes Aggravates Collagenase-Induced Intracerebral Hemorrhagic Injury
Qasim M. Alhadidi, Kevin M. Nash, Ghaith A. Bahader, Emily Zender, Marcia F. McInerney, Zahoor A. Shah Biomedicines.2024; 12(8): 1867. CrossRef - Astrocyte involvement in metabolic regulation and disease
Muhammad Naveed, Kathryn Smedlund, Qi-Gang Zhou, Weikang Cai, Jennifer W. Hill Trends in Endocrinology & Metabolism.2024;[Epub] CrossRef - Targeting ferroptosis in the neurovascular unit: A promising approach for treating diabetic cognitive impairment
Wenlan Zhang, Yijing Yan, Chunmei Yi, Xijuan Jiang, Lin Guo, Shanshan Huang, Tong Xia, Fayin Huang, Yike Jiao, Huhu Li, Bin Yu, Yongna Dai International Immunopharmacology.2024; 142: 113146. CrossRef - Neurometabolic substrate transport across brain barriers in diabetes mellitus: Implications for cognitive function and neurovascular health
Ritwick Mondal, Shramana Deb, Dipanjan Chowdhury, Shramana Sarkar, Aakash Guha Roy, Gourav Shome, Vramanti Sarkar, Durjoy Lahiri, Julián Benito-León Neuroscience Letters.2024; 843: 138028. CrossRef - Protective effects of berberine against diabetes-associated cognitive decline in mice
Mrinal Gupta, Mohammad Rumman, Babita Singh, Shivani Pandey Acta Diabetologica.2024;[Epub] CrossRef - The NG2-glia is a potential target to maintain the integrity of neurovascular unit after acute ischemic stroke
Xiaoyan Hu, Panpan Geng, Xiaoyun Zhao, Qian Wang, Changqing Liu, Chun Guo, Wen Dong, Xinchun Jin Neurobiology of Disease.2023; 180: 106076. CrossRef - Tight junction disruption and the pathogenesis of the chronic complications of diabetes mellitus: A narrative review
Ma Ludivina Robles-Osorio, Ernesto Sabath World Journal of Diabetes.2023; 14(7): 1013. CrossRef - Function and therapeutic value of astrocytes in diabetic cognitive impairment
Fanyu Meng, Jiafeng Fu, Lin Zhang, Mengqing Guo, Pengwei Zhuang, Qingsheng Yin, Yanjun Zhang Neurochemistry International.2023; 169: 105591. CrossRef - Exploring the Molecular Targets for Type 2 Diabetes-Induced Alzheimer’s Disease Through Bioinformatics Analysis
Lin Gao, Chengyu Huang, Hui Li, Shidi Wu, Xiaoyan Zhou, Changjiang Ying Epigenomics.2023; 15(11): 619. CrossRef - In vivo retinal imaging is associated with cognitive decline, blood-brain barrier disruption and neuroinflammation in type 2 diabetic mice
May Majimbi, Samuel McLenachan, Michael Nesbit, Fred K. Chen, Virginie Lam, John Mamo, Ryu Takechi Frontiers in Endocrinology.2023;[Epub] CrossRef - Diabetic microvascular disease in non-classical beds: the hidden impact beyond the retina, the kidney, and the peripheral nerves
Dídac Mauricio, Mònica Gratacòs, Josep Franch-Nadal Cardiovascular Diabetology.2023;[Epub] CrossRef - Transcranial photobiomodulation improves insulin therapy in diabetic microglial reactivity and the brain drainage system
Shaojun Liu, Dongyu Li, Tingting Yu, Jingtan Zhu, Oxana Semyachkina-Glushkovskaya, Dan Zhu Communications Biology.2023;[Epub] CrossRef - NG2‐glia crosstalk with microglia in health and disease
Zuo Zhang, Xiaolong Li, Hongli Zhou, Jiyin Zhou CNS Neuroscience & Therapeutics.2022; 28(11): 1663. CrossRef - Accelerated amyloid angiopathy and related vascular alterations in a mixed murine model of Alzheimer´s disease and type two diabetes
Maria Vargas-Soria, Juan Jose Ramos-Rodriguez, Angel del Marco, Carmen Hierro-Bujalance, Maria Jose Carranza-Naval, Maria Calvo-Rodriguez, Susanne J. van Veluw, Alan W. Stitt, Rafael Simó, Brian J. Bacskai, Carmen Infante-Garcia, Monica Garcia-Alloza Fluids and Barriers of the CNS.2022;[Epub] CrossRef
- Basic Research
- NG2-Glia Cause Diabetic Blood-Brain Barrier Disruption by Secreting MMP-9
-
Xiaolong Li, Yan Cai, Zhu Zhong, Maolin Li, Dong Huang, Zhifei Qiao, Hongli Zhou, Zuo Zhang, Jiyin Zhou
-
Received September 25, 2023 Accepted February 22, 2024 Published online July 23, 2024
-
DOI: https://doi.org/10.4093/dmj.2023.0342
[Epub ahead of print]
-
-
Abstract
PDFPubReader ePub
- Background
Disorders of the blood-brain barrier (BBB) arising from diabetes mellitus are closely related to diabetic encephalopathy. Previous research has suggested that neuron-glia antigen 2 (NG2)-glia plays a key role in maintaining the integrity of the BBB. However, the mechanism by which NG2-glia regulates the diabetic BBB remains unclear.
Methods Type 2 diabetes mellitus (T2DM) db/db mice and db/m mice were used. Evans-Blue BBB permeability tests and transmission electron microscopy techniques were applied. Tight junction proteins were assessed by immunofluorescence and transmission electron microscopy. NG2-glia number and signaling pathways were evaluated by immunofluorescence. Detection of matrix metalloproteinase-9 (MMP-9) in serum was performed using enzyme-linked immunosorbent assay (ELISA).
Results In T2DM db/db mice, BBB permeability in the hippocampus significantly increased from 16 weeks of age, and the structure of tight junction proteins changed. The number of NG2-glia in the hippocampus of db/db mice increased around microvessels from 12 weeks of age. Concurrently, the expression of MMP-9 increased in the hippocampus with no change in serum. Sixteen- week-old db/db mice showed activation of the Wnt/β-catenin signaling in hippocampal NG2-glia. Treatment with XAV-939 improved structural and functional changes in the hippocampal BBB and reduced MMP-9 secretion by hippocampal NG2-glia in db/db mice. It was also found that the upregulation of β-catenin protein in NG2-glia in the hippocampus of 16-week-old db/db mice was significantly alleviated by treatment with XAV-939.
Conclusion The results indicate that NG2-glia can lead to structural and functional disruption of the diabetic BBB by activating Wnt/β-catenin signaling, upregulating MMP-9, and degrading tight junction proteins.
|