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Citations to this article

Hypoglycemic neuronal death is triggered by glucose reperfusion and activation of neuronal NADPH oxidase
Sang Won Suh, … , Pak H. Chan, Raymond A. Swanson
Sang Won Suh, … , Pak H. Chan, Raymond A. Swanson
Published April 2, 2007
Citation Information: J Clin Invest. 2007;117(4):910-918. https://doi.org/10.1172/JCI30077.
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Research Article Article has an altmetric score of 11

Hypoglycemic neuronal death is triggered by glucose reperfusion and activation of neuronal NADPH oxidase

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Abstract

Hypoglycemic coma and brain injury are potential complications of insulin therapy. Certain neurons in the hippocampus and cerebral cortex are uniquely vulnerable to hypoglycemic cell death, and oxidative stress is a key event in this cell death process. Here we show that hypoglycemia-induced oxidative stress and neuronal death are attributable primarily to the activation of neuronal NADPH oxidase during glucose reperfusion. Superoxide production and neuronal death were blocked by the NADPH oxidase inhibitor apocynin in both cell culture and in vivo models of insulin-induced hypoglycemia. Superoxide production and neuronal death were also blocked in studies using mice or cultured neurons deficient in the p47phox subunit of NADPH oxidase. Chelation of zinc with calcium disodium EDTA blocked both the assembly of the neuronal NADPH oxidase complex and superoxide production. Inhibition of the hexose monophosphate shunt, which utilizes glucose to regenerate NADPH, also prevented superoxide formation and neuronal death, suggesting a mechanism linking glucose reperfusion to superoxide formation. Moreover, the degree of superoxide production and neuronal death increased with increasing glucose concentrations during the reperfusion period. These results suggest that high blood glucose concentrations following hypoglycemic coma can initiate neuronal death by a mechanism involving extracellular zinc release and activation of neuronal NADPH oxidase.

Authors

Sang Won Suh, Elizabeth T. Gum, Aaron M. Hamby, Pak H. Chan, Raymond A. Swanson

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 Total
Citations: 5 7 4 11 9 9 6 11 11 9 11 16 6 15 9 11 9 7 2 168
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article in year 2015 (11)

Title and authors Publication Year
Inhibition of NADPH oxidase activation reduces EAE-induced white matter damage in mice
BY Choi, JH Kim, AR Kho, IY Kim, SH Lee, BE Lee, E Choi, M Sohn, M Stevenson, TN Chung, TM Kauppinen, SW Suh
Journal of Neuroinflammation 2015
Protection of hypoglycemia-induced neuronal death by β-hydroxybutyrate involves the preservation of energy levels and decreased production of reactive oxygen species
A Julio-Amilpas, T Montiel, E Soto-Tinoco, C Gerónimo-Olvera, L Massieu
Journal of Cerebral Blood Flow & Metabolism 2015
Two-Dimensional Zymography Differentiates Gelatinase Isoforms in Stimulated Microglial Cells and in Brain Tissues of Acute Brain Injuries
S Chen, F Meng, Z Chen, BN Tomlinson, JM Wesley, GY Sun, AT Whaley-Connell, JR Sowers, J Cui, Z Gu, Y St-Pierre
PloS one 2015
Induction of a Proinflammatory Response in Cortical Astrocytes by the Major Metabolites Accumulating in HMG-CoA Lyase Deficiency: the Role of ERK Signaling Pathway in Cytokine Release
CG Fernandes, MD Rodrigues, B Seminotti, AL Colín-González, A Santamaria, A Quincozes-Santos, M Wajner
Molecular Neurobiology 2015
Associations between dynamics of the blood glucose level after hypoglycemia and intensive care unit mortality: a retrospective multicenter study
RT van Hooijdonk, JM Binnekade, A Abu–Hanna, FB Houckgeest, LS Hofstra, J Horn, MA Kuiper, NP Juffermans, HL van Oever, JP van der Sluijs, PE Spronk, MJ Schultz
Intensive Care Medicine 2015
Effects of Alda-1, an Aldehyde Dehydrogenase-2 Agonist, on Hypoglycemic Neuronal Death
T Ikeda, T Takahashi, M Tsujita, M Kanazawa, M Toriyabe, M Koyama, K Itoh, T Nakada, M Nishizawa, T Shimohata, MF Essop
PloS one 2015
White matter hyperintensities in middle-aged adults with childhood-onset type 1 diabetes
KA Nunley, CM Ryan, TJ Orchard, HJ Aizenstein, JR Jennings, J Ryan, JC Zgibor, RM Boudreau, T Costacou, JD Maynard, RG Miller, C Rosano
Neurology 2015
Hypothalamic-Pituitary-Adrenal Axis Programming after Recurrent Hypoglycemia during Development
R Rao
Journal of Clinical Medicine 2015
Neonatal Glycemia and Neurodevelopmental Outcomes at 2 Years
CJ McKinlay, JM Alsweiler, JM Ansell, NS Anstice, JG Chase, GD Gamble, DL Harris, RJ Jacobs, Y Jiang, N Paudel, M Signal, B Thompson, TA Wouldes, TY Yu, JE Harding
New England Journal of Medicine 2015
Diabetes Mellitus, Obesity, and Diagnosis of Amyotrophic Lateral Sclerosis: A Population-Based Study
MA Kioumourtzoglou, RS Rotem, RM Seals, O Gredal, J Hansen, MG Weisskopf
JAMA NEUROL 2015
The emerging neuroprotective role of mitochondrial uncoupling protein-2 in traumatic brain injury
KP Normoyle, M Kim, A Farahvar, D Llano, K Jackson, H Wang
Translational Neuroscience 2015

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