Evaluating blood-brain barrier permeability in a rat model of type 2 diabetes

• Published in: Journal of translational medicine Vol. 18; no. 1; p. 256
• Main Authors: Qiao, Ju, Lawson, Christopher M, Rentrup, Kilian F G, Kulkarni, Praveen, Ferris, Craig F
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 24.06.2020; BioMed Central; BMC
• Subjects: Animals; BBZDR/Wor rat; Blood; Blood-Brain Barrier; Brain - diagnostic imaging; Brain research; Capillary Permeability; Cerebellum; Contrast enhanced (QUTE-CE); Datasets; Dementia; Dementia disorders; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2; Diabetes therapy; Diabetic encephalopathy; Dopamine receptors; Encephalopathy; Ferumoxytol; Insulin; Laboratory animals; Magnetic Resonance Imaging; Medical imaging; Medical research; Membrane permeability; Mesencephalon; Methodology; Neuroimaging; Permeability; Quantitative ultrashort time-to-echo; Rats; Rodents; Small vessel disease; Studies; Type 2 diabetes; United States > US; Quantitative ultrashort time-to-echo; Vascular biomarker; Magnetic resonance imaging; Small vessel disease; BBZDR/Wor rat; Diabetic encephalopathy; Ferumoxytol; Contrast enhanced (QUTE-CE)
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/s12967-020-02428-3

This is an exploratory study using a novel imaging modality, quantitative ultrashort time-to-echo, contrast enhanced (QUTE-CE) magnetic resonance imaging to evaluate the permeability of the blood-brain barrier in a rat model of type 2 diabetes with the presumption that small vessel disease is a contributing factor to neuropathology in diabetes. The BBZDR/Wor rat, a model of type 2 diabetes, and age-matched controls were studied for changes in blood-brain barrier permeability. QUTE-CE, a quantitative vascular biomarker, generated angiographic images with over 500,000 voxels that were registered to a 3D MRI rat brain atlas providing site-specific information on blood-brain barrier permeability in 173 different brain areas. In this model of diabetes, without the support of insulin treatment, there was global capillary pathology with over 84% of the brain showing a significant increase in blood-brain barrier permeability over wild-type controls. Areas of the cerebellum and midbrain dopaminergic system were not significantly affected. Small vessel disease as assessed by permeability in the blood-brain barrier in type 2 diabetes is pervasive and includes much of the brain. The increase in blood-brain barrier permeability is a likely contributing factor to diabetic encephalopathy and dementia.