ArticleJournal of neuroinflammation2012
Recurrent/moderate hypoglycemia induces hippocampal dendritic injury, microglial activation, and cognitive impairment in diabetic rats.
Article in Journal of neuroinflammation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
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Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 97 citations in OpenAlex.
- Effects of diabetes on microglial physiology: a systematic review of in vitro, preclinical and clinical studies.Journal of neuroinflammation · 2023Pooled it
- The cognitive consequences of hypoglycemia in diabetes.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026Review
- 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
- Lipid-lowering and glucose-lowering drug targets differentially modulate antipsychotic treatment efficacy in schizophrenia.Cell reports. Medicine · 2026Article
- Hypoglycemia aggravates cognitive degeneration by activating endothelial ZBP1-mediated PANoptosis in type 2 diabetic mice.Frontiers in pharmacology · 2026Article
- Initial treatment for uncontrolled type 2 diabetes: A clinical trial comparing basal insulin and modified-release gliclazide.Caspian journal of internal medicine · 2026Article
- Immunometabolic reprogramming of central and peripheral immune cells in mental disorders: mechanisms and therapeutic implications.Frontiers in immunology · 2026Review
- The metabolic engine of cognition: microglia-neuron interactions in health, ageing and disease.Nature metabolism · 2025Review
- A Small-Molecule TrkB/TrkC Ligand Promotes Neurogenesis and Behavioral Recovery Following Traumatic Brain Injury.Neurotrauma reports · 2025Article
- Extracellular vesicles released from microglia after palmitate exposure impact brain function.Journal of neuroinflammation · 2024Article
- Effect of recurrent severe insulin-induced hypoglycemia on the cognitive function and brain oxidative status in the rats.Diabetology & metabolic syndrome · 2024Article
- Article
- D-ꞵ-hydroxybutyrate stabilizes hippocampal CA3-CA1 circuit during acute insulin resistance.PNAS nexus · 2024Article
- Acute severe hypoglycemia alters mouse brain microvascular proteome.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024Article
- Article
- Dose-Dependent Beneficial Effect of Ketone Supplement-Evoked Ketosis on Anxiety Level in Female WAG/Rij Rats: Sometimes Less Is More.Nutrients · 2023Article
- Corresponding risk factors between cognitive impairment and type 1 diabetes mellitus: A narrative review.Heliyon · 2022Review
- The Role of NADPH Oxidase in Neuronal Death and Neurogenesis after Acute Neurological Disorders.Antioxidants (Basel, Switzerland) · 2021Review
- Insulin actions on hypothalamic glucose-sensing neurones.Journal of neuroendocrinology · 2021Review
- Sleep Disturbances and Cognitive Impairment in the Course of Type 2 Diabetes-A Possible Link.Current neuropharmacology · 2021Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundRecurrent/moderate (R/M) hypoglycemia is common in type 1 diabetes. Although mild or moderate hypoglycemia is not life-threatening, if recurrent, it may cause cognitive impairment. In the present study, we sought to determine whether R/M hypoglycemia leads to neuronal death, dendritic injury, or cognitive impairment.
methodsThe experiments were conducted in normal and in diabetic rats. Rats were subjected to moderate hypoglycemia by insulin without anesthesia. Oxidative stress was evaluated by 4-Hydroxy-2-nonenal immunostaining and neuronal death was determined by Fluoro-Jade B staining 7 days after R/M hypoglycemia. To test whether oxidative injury caused by NADPH oxidase activation, an NADPH oxidase inhibitor, apocynin, was used. Cognitive function was assessed by Barnes maze and open field tests at 6 weeks after R/M hypoglycemia.
resultsThe present study found that oxidative injury was detected in the dendritic area of the hippocampus after R/M hypoglycemia. Sparse neuronal death was found in the cortex, but no neuronal death was detected in the hippocampus. Significant cognitive impairment and thinning of the CA1 dendritic region was detected 6 weeks after hypoglycemia. Oxidative injury, cognitive impairment, and hippocampal thinning after R/M hypoglycemia were more severe in diabetic rats than in non-diabetic rats. Oxidative damage in the hippocampal CA1 dendritic area and microglial activation were reduced by the NADPH oxidase inhibitor, apocynin.
conclusionThe present study suggests that oxidative injury of the hippocampal CA1 dendritic region by R/M hypoglycemia is associated with chronic cognitive impairment in diabetic patients. The present study further suggests that NADPH oxidase inhibition may prevent R/M hypoglycemia-induced hippocampal dendritic injury.
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