One of the limiting factors in stroke therapeutic development is the use of animal models that do not well represent the underlying medical conditions of patients. In humans, diabetes increases the risk of stroke incidence as well as post-stroke mortality. To understand the mechanisms that render diabetics to increased brain damage, we evaluated the effect of transient middle cerebral artery occlusion in adult db/db mice. The db/db mouse is a model of type-2 diabetes with four times higher blood sugar than its normoglycemic genetic control(db/+ mouse). Following transient middle cerebral artery occlusion, the db/db mice showed significantly higher mortality, bigger infarcts, increased cerebral edema, worsened neurological status compared to db/+ mice. The db/db mice also showed significantly higher post-ischemic inflammatory markers (ICAM1(+) capillaries, extravasated macrophages/neutrophils and exacerbated proinflammatory gene expression) compared to db/+ mice. In addition, the post-ischemic neuroprotective heat-shock chaperone gene expression was curtailed in the db/db compared to db/+ mice.© 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

We studied the association of stroke severity with survival from 1 month to 10 years after stroke and explored how stroke severity interacts with other prognostic indicators with time. The study is based on 999 stroke patients from the community-based Copenhagen Stroke Study (mean age, 74.3±11.0 years; 56% women; mean Scandinavian Stroke Scale [SSS], 38.0±17.4). Evaluation included stroke severity (based on the SSS), computed tomography scan, and a cardiovascular risk profile. Using logistic regression models, we examined the relevance of the SSS on mortality at 1 month and 1, 5, and 10 years. We analyzed the proportion of the variation explained by the models and bias of risk factors estimates with and without the SSS in the model. Mortality rate was 16.6% at 1 month, 31.5% at 1 year, 60.2% at 5 years, and 81.3% at 10 years. In models including the SSS, 22.4%, 20.9%, 32.8%, and 39.5% of the variance was explained for the endpoints of 1 month, 1 year, 5 years, and 10 years, respectively. When SSS was left out of the model, the corresponding values were 6.9%, 13.3%, 29.0%, and 35.1%. Factors significantly associated with survival were SSS at 1 month; SSS, age, diabetes, and stroke type at 1 year; SSS, age, sex, previous stroke, other complicating diseases, diabetes, smoking, and atrial fibrillation at 5 years; and SSS, age, sex, other complicating diseases, and diabetes at 10 years. Our data suggest that stroke severity is significantly associated with short-term and long-term survival. It is the all-important predictor of short-term survival, whereas it is of less importance in predicting long-term survival.Copyright © 2011 National Stroke Association. Published by Elsevier Inc. All rights reserved.

The impact of prediabetes and diabetes on stroke and the development of dementia after a stroke remain unclear.A total of 2655 dementia-free participants (including a stroke-free cohort and a prevalent stroke cohort) were followed-up for 12 years. Dementia and post-stroke dementia were determined by clinical examinations and national registry data. Diabetes was ascertained via medical examination, medication use, medical records, or glycated hemoglobin (HbA1c) ≥6.5%. Prediabetes was defined as HbA1c ≥5.7% in diabetes-free participants.In the stroke-free cohort, 236 participants developed ischemic stroke, and 47 developed post-stroke dementia. Diabetes was associated with ischemic stroke (hazard ratio [HR] 1.76, 95% confidence interval [CI] 1.16 to 2.67) and post-stroke dementia (HR 2.56, 95% CI 1.04 to 6.25). In the prevalent stroke cohort, diabetes was also related to dementia risk. Prediabetes was not significantly related to stroke or post-stroke dementia.Diabetes, but not prediabetes, is associated with an increased risk of ischemic stroke and post-stroke dementia.© 2020 The Authors. Alzheimer's & Dementia published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association.

To evaluate the possible early consequences of impaired glucose metabolism on the brain by assessing the relationship of diabetes, fasting blood glucose (FBG) levels, and insulin resistance with cognitive performance and brain integrity in healthy young and middle-aged adults.The sample included dementia-free participants (mean age 40 ± 9 years; 53% women) of the Framingham Heart Study third-generation cohort with cognitive testing of memory, abstract reasoning, visual perception, attention, and executive function (n = 2,126). In addition, brain MRI examination (n = 1,597) was used to determine white matter, gray matter, and white matter hyperintensity (WMH) volumes and fractional anisotropy measures. We used linear regression models to assess relationships between diabetes, FBG, and insulin resistance with cognition, lobar gray matter, and WMH volumes as well as voxel-based microstructural white matter integrity and gray matter density, adjusting for potential confounders. Mediating effect of brain lesions on the association of diabetes with cognitive performance was also tested.Diabetes was associated with worse memory, visual perception, and attention performance; increased WMH; and decreased total cerebral brain and occipital lobar gray matter volumes. The link of diabetes with attention and memory was mediated through occipital and frontal atrophy, and the latter also through hippocampal atrophy. Both diabetes and increased FBG were associated with large areas of reductions in gray matter density and fractional anisotropy on voxel-based analyses.We found that hyperglycemia is associated with subtle brain injury and impaired attention and memory even in young adults, indicating that brain injury is an early manifestation of impaired glucose metabolism.© 2015 American Academy of Neurology.

Background and Purpose-Type 2 diabetes mellitus (T2DM) is associated with diseases of the brain, kidney, and vasculature. However, the relationship between T2DM, chronic kidney disease, brain alterations, and cognitive function after stroke is unknown. We aimed to evaluate the inter-relationship between T2DM, impaired renal function, brain pathology on imaging, and cognitive decline in a longitudinal poststroke cohort.Methods-The TABASCO (Tel Aviv brain acute stroke cohort) is a prospective cohort of stroke/transient ischemic attack survivors. The volume and white matter integrity, ischemic lesions, and brain and hippocampal volumes were measured at baseline using 3-T MRI. Cognitive tests were performed on 507 patients, who were diagnosed as having mild cognitive impairment, dementia, or being cognitively intact after 24 months.Results-At baseline, T2DM and impaired renal function (estimated creatinine clearance [eCCl] <60 mL/min) were associated with smaller brain and hippocampal volumes, reduced cortical thickness, and worse white matter microstructural integrity. Two years later, both T2DM and eCCl <60 mL/min were associated with poorer cognitive scores, and 19.7% of the participants developed cognitive decline (mild cognitive impairment or dementia). Multiple analysis, controlling for age, sex, education, and apolipoprotein E4, showed a significant association of both T2DM and eCCl <60 mL/min with cognitive decline. Having both conditions doubled the risk compared with patients with T2DM or eCCl <60 mL/min alone and almost quadrupled the risk compared with patients without either abnormality.Conclusions-T2DM and impaired renal function are independently associated with abnormal brain structure, as well as poorer performance in cognitive tests, 2 years after stroke. The presence of both conditions quadruples the risk for cognitive decline. T2DM and lower eCCl have an independent and additive effect on brain atrophy and the risk of cognitive decline.