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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.