ArticlePloS one2014
Diabetes mellitus aggravates hemorrhagic transformation after ischemic stroke via mitochondrial defects leading to endothelial apoptosis.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 66 citations in OpenAlex.
- Association of Glycated Hemoglobin (HbA1c) with Functional Outcomes After Endovascular Thrombectomy for Acute Ischemic Stroke.Clinical interventions in aging · 2026Article
- Impact of Diabetes on Oxidative Stress, Mitochondrial Function, and Neurological Outcomes Following Ischemic Stroke: A Sex-Based Experimental Analysis.Molecular neurobiology · 2025Article
- LncRNA-MEG3 Mediated Diabetic Cerebral Ischemia-Reperfusion Injury-Induced Apoptosis via Modulating Interaction Between Annexin A2 and Akt in Mitochondria.CNS neuroscience & therapeutics · 2025Article
- Predictive Modeling of Symptomatic Intracranial Hemorrhage Following Endovascular Thrombectomy: Insights From the Nationwide TREAT-AIS Registry.Journal of stroke · 2025Article
- Hyperglycemia enhances brain susceptibility to lipopolysaccharide-induced neuroinflammation via astrocyte reprogramming.Journal of neuroinflammation · 2024Article
- MicroRNA Regulatory Pattern in Diabetic Mouse Cortex at Different Stages Following Ischemic Stroke.Journal of molecular neuroscience : MN · 2024Article
- Mitochondrial Dysfunction in Endothelial Progenitor Cells: Unraveling Insights from Vascular Endothelial Cells.Biology · 2024Review
- Exacerbated VEGF up-regulation accompanies diabetes-aggravated hemorrhage in mice after experimental cerebral ischemia and delayed reperfusion.Neural regeneration research · 2022Article
- Review
- Intracellular MUC20 variant 2 maintains mitochondrial calcium homeostasis and enhances drug resistance in gastric cancer.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2022Article
- Reduction of lactoferrin aggravates neuronal ferroptosis after intracerebral hemorrhagic stroke in hyperglycemic mice.Redox biology · 2022Article
- Early-phase administration of human amnion-derived stem cells ameliorates neurobehavioral deficits of intracerebral hemorrhage by suppressing local inflammation and apoptosis.Journal of neuroinflammation · 2022Article
- Hyperglycemia in acute ischemic stroke: physiopathological and therapeutic complexity.Neural regeneration research · 2022Review
- Association of hypocalcemia with in-hospital mortality in critically ill patients with intracerebral hemorrhage: A retrospective cohort study.Frontiers in neurology · 2022Article
- Association Between Raised HbA1c Levels and Hemorrhagic Transformation in Patients With Ischemic Stroke.Cureus · 2021Article
- Loss of MIC60 Aggravates Neuronal Death by Inducing Mitochondrial Dysfunction in a Rat Model of Intracerebral Hemorrhage.Molecular neurobiology · 2021Article
- Article
- Melatonin Ameliorates Hemorrhagic Transformation via Suppression of ROS-Induced NLRP3 Activation after Cerebral Ischemia in Hyperglycemic Rats.Oxidative medicine and cellular longevity · 2021Article
- Impact of aging and comorbidities on ischemic stroke outcomes in preclinical animal models: A translational perspective.Experimental neurology · 2021Review
- Immune-Inflammatory, Metabolic, Oxidative, and Nitrosative Stress Biomarkers Predict Acute Ischemic Stroke and Short-Term Outcome.Neurotoxicity research · 2020Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Diabetes is a crucial risk factor for stroke and is associated with increased frequency and poor prognosis. Although endothelial dysfunction is a known contributor of stroke, the underlying mechanisms have not been elucidated. The aim of this study was to elucidate the mechanism by which chronic hyperglycemia may contribute to the worsened prognosis following stroke, especially focusing on mitochondrial alterations. We examined the effect of hyperglycemia on hemorrhagic transformation at 24 hours after middle cerebral artery occlusion (MCAO) in streptozotocin (STZ) -induced diabetic mice. We also examined the effects of high-glucose exposure for 6 days on cell death, mitochondrial functions and morphology in human brain microvascular endothelial cells (HBMVECs) or human endothelial cells derived from induced pluripotent stem cells (iCell endothelial cells). Hyperglycemia aggravated hemorrhagic transformation, but not infarction following stroke. High-glucose exposure increased apoptosis, capase-3 activity, and release of apoptosis inducing factor (AIF) and cytochrome c in HBMVECs as well as affected mitochondrial functions (decreased cell proliferation, ATP contents, mitochondrial membrane potential, and increased matrix metalloproteinase (MMP)-9 activity, but not reactive oxygen species production). Furthermore, morphological aberration of mitochondria was observed in diabetic cells (a great deal of fragmentation, vacuolation, and cristae disruption). A similar phenomena were seen also in iCell endothelial cells. In conclusion, chronic hyperglycemia aggravated hemorrhagic transformation after stroke through mitochondrial dysfunction and morphological alteration, partially via MMP-9 activation, leading to caspase-dependent apoptosis of endothelial cells of diabetic mice. Mitochondria-targeting therapy may be a clinically innovative therapeutic strategy for diabetic complications in the future.
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