ArticleMolecular neurobiology2019
Hyperglycemia-Driven Neuroinflammation Compromises BBB Leading to Memory Loss in Both Diabetes Mellitus (DM) Type 1 and Type 2 Mouse Models.
Article in Molecular neurobiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 192 papers, 5 of them syntheses that pooled it.
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Who cites it
192 citing papers in PubMed, 5 syntheses or guidelines pooled it, 317 citations in OpenAlex.
- Effect of glycemic control on cognitive function in patients with type 1 diabetes mellitus: a systematic review and meta-analysis.Systematic reviews · 2024Pooled it
- Effects of diabetes on microglial physiology: a systematic review of in vitro, preclinical and clinical studies.Journal of neuroinflammation · 2023Pooled it
- Blood glucose level affects prognosis of patients who received intravenous thrombolysis after acute ischemic stroke? A meta-analysis.Frontiers in endocrinology · 2023Pooled it
- Vascular risk factors for idiopathic normal pressure hydrocephalus: a systematic review and meta-analysis.Frontiers in neurology · 2023Pooled it
- Cardiometabolic risk factors and brain age: a meta-analysis to quantify brain structural differences related to diabetes, hypertension, and obesity.Journal of psychiatry & neuroscience : JPNPooled it
- Detrimental Effect of Acute Hyperglycemia on the Outcomes of Large Ischemic Region Stroke.Journal of the American Heart Association · 2024Trial
- The third Intensive Care Bundle with Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT3): an international, stepped wedge cluster randomised controlled trial.Lancet (London, England) · 2023Trial
- Diabetic cerebral microvascular disorder: from key pathologies to targeted interventions.Annals of medicine · 2026Review
- Metabolic reprogramming in diabetic panvascular disease: Molecular mechanism and therapeutic strategies.iScience · 2026Review
- Thalamic Nuclei Atrophy in Type 1 Diabetes Mellitus Across Disease Duration.Journal of magnetic resonance imaging : JMRI · 2026Article
- High Glucose Alters Extracellular Vesicle Protein Composition and Promotes EV-Mediated Monocyte Adhesion to Endothelial Cells.International journal of molecular sciences · 2026Article
- A peripheral perspective on brain health: vascular and skeletal muscle contributions.American journal of physiology. Heart and circulatory physiology · 2026Review
- Blood-brain barrier water permeability is elevated in type 2 diabetes and obesity: associations with cognitive function and metabolic markers.Fluids and barriers of the CNS · 2026Article
- The Interaction Between Insulin Resistance and Neuroinflammation in the Brain and Its Impact on Diabetic Encephalopathy.Biology · 2026Review
- Diabetes reprograms brain and systemic immune landscapes to impair repair after injury.Molecular brain · 2026Article
- Futile recanalization after mechanical thrombectomy in patients with acute ischemic stroke and large ischemic core.Journal of cerebrovascular and endovascular neurosurgery · 2026Article
- Association between stress hyperglycemia ratio and cognitive function in older patients with diabetes or prediabetes: a cross-sectional study from the NHANES.Endocrine journal · 2026Article
- Thrombin is increased in diabetic retinal pathology in the STZ mice model, and its attenuation by a specific inhibitor, PARIN5, is associated with preserved function.Scientific reports · 2026Article
- Blood-Brain Barrier Permeability Is Elevated in Type 2 Diabetes and Obesity: Associations with Cognitive Function and Metabolic Markers.Research square · 2026Article
- Extracellular Vesicles as Mediators of Endothelial and Tubular Injury in Cardiac Surgery-Associated Acute Kidney Injury.Biomedicines · 2026Review
132 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
End organ injury in diabetes mellitus (DM) is driven by microvascular compromise (including diabetic retinopathy and nephropathy). Cognitive impairment is a well-known complication of DM types 1 and 2; however, its mechanism(s) is(are) not known. We hypothesized that blood-brain barrier (BBB) compromise plays a key role in cognitive decline in DM. Using a DM type 1 model (streptozotocin injected C57BL/6 mice) and type 2 model (leptin knockout obese db/db mice), we showed enhanced BBB permeability and memory loss (Y maze, water maze) that are associated with hyperglycemia. Gene profiling in isolated microvessels from DM type 1 animals demonstrated deregulated expression of 54 genes related to angiogenesis, inflammation, vasoconstriction/vasodilation, and platelet activation pathways by at least 2-fold (including eNOS, TNFα, TGFβ1, VCAM-1, E-selectin, several chemokines, and MMP9). Further, the magnitude of gene expression was linked to degree of cognitive decline in DM type 1 animals. Gene analysis in brain microvessels of DM type 2 db/db animals showed alterations of similar genes as in DM 1 model, some to an even greater extent. Neuropathologic analyses of brain tissue derived from DM mice showed microglial activation, expression of ICAM-1, and attenuated coverage of pericytes compared to controls. There was a significant upregulation of inflammatory genes in brain tissue in both DM models. Taken together, our findings indicate that BBB compromise in DM in vivo models and its association with memory deficits, gene alterations in brain endothelium, and neuroinflammation. Prevention of BBB injury may be a new therapeutic approach to prevent cognitive demise in DM.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.