Selective vulnerability of brain regions to oxidative stress in a non-coma model of insulin-induced hypoglycemia

doi:10.1016/j.neuroscience.2009.10.003

Neuroscience

Volume 165, Issue 1, 13 January 2010, Pages 28-38

https://doi.org/10.1016/j.neuroscience.2009.10.003 Get rights and content

Abstract

Insulin-induced hypoglycemia causes the death of neurons in particular brain regions including the cerebral cortex, the striatum and the hippocampus, while the cerebellum and the brain stem are more resistant. The mechanisms underlying this selective vulnerability to hypoglycemic damage are unknown. In the present study we have analyzed the presence of lipoperoxidation products and nitrosilated protein residues in different rat brain regions during and after the induction of hypoglycemia. Insulin-injected hypoglycemic rats were sacrificed before the onset of the isoelectric period or infused with glucose to end hypoglycemia, and then sacrificed at different times. Increased lipoperoxidation levels were observed before the onset of the isoelectric period, while 3-nitrotyrosine (NT) residues in proteins and NT-positive cells were only observed after glucose reperfusion. These changes were found only in vulnerable brain regions, while none of them was evident in the cerebellum, suggesting a correlation between oxidative damage and vulnerability to hypoglycemic neuronal death in selective brain regions. Results suggest that a pro-oxidant state is promoted in certain brain regions during hypoglycemia and after the glucose reperfusion phase, which might result from the activation of several oxidative stress pathways and may be related to subsequent cell death.

Section snippets

Experimental procedures

Male Wistar rats (320–380 g) obtained from the animal house at the Instituto de Fisiología Celular (Universidad Nacional Autónoma de México) were used throughout the study. They were handled according with the National Institute of Health Guide for the Care and Use of Laboratory Animals (NIH Publications No. 80-23) revised 1996, and with the local Animal Care Committee approval. All efforts were made to minimize the number of animals used and their suffering. Rats were housed under controlled

Results

The electroencephalographic brain activity was recorded before (control) and during the hypoglycemic condition. A representative recording is shown in Fig. 1. Normal activity is still observed 1 h after insulin administration even though glucose levels are low, as shown in Fig. 2. Approximately 2 h after insulin injection, electrical brain activity is impaired and high amplitude and low frequency waves appear (Fig. 1 line 3), as described by others (Auer et al., 1984a). At this stage animals

Discussion

Intensive insulin therapy in patients with type 1 diabetes mellitus is commonly associated with hypoglycemia. Patients might suffer from symptomatic hypoglycemia as frequently as twice per week and from one episode of severe hypoglycemia per year (Cryer, 2004, Cryer, 2007). In addition, an impaired counter-regulatory response to hypoglycemia is frequently associated with the presence of hypoglycemic episodes in type 1 diabetic patients (Jones and Davis, 2003, Cryer, 2006). Acute brain

Acknowledgments

This work was supported by CONACyT 48645-Q grant to L. Massieu and 181312 CONACyT scholarship to M.L. Haces. The authors thank Mrs. Araceli Patrón and Mr. Gabriel Horijuelas for their help in microscopy image analysis. This study was performed in partial fulfillment of the requirements for the PhD degree in Biomedical Sciences of M.L. Haces at the Universidad Nacional Autónoma de México.

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Cellular NeuroscienceResearch PaperSelective vulnerability of brain regions to oxidative stress in a non-coma model of insulin-induced hypoglycemia

Abstract

Section snippets

Experimental procedures

Results

Discussion

Acknowledgments

Behav Brain Res

Trends Endocrinol Metab

Anal Biochem

Prog Neurobiol

Brain Res

Neurobiol Dis

Epilepsy Res

Exp Neurol

Free Radic Biol Med

Neurosci Lett

Repeated hypoglycemia and cognitive declineA case report

Neuro Endocrinol Lett

Progress review: hypoglycemic brain damage

Stroke

The temporal evolution of hypoglycemic brain damageI. Light- and electron-microscopic findings in the rat cerebral cortex

Acta Neuropathol

The temporal evolution of hypoglycemic brain damageII. Light- and electron-microscopic findings in the hippocampal gyrus and subiculum of the rat

Acta Neuropathol

Hypoglycemic brain injury in the ratCorrelation of density of brain damage with the EEG isoelectric time: a quantitative study

Diabetes

The distribution of hypoglycemic brain damage

Acta Neuropathol

Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and the ugly

Am J Physiol

Effect of starvation and insulin-induced hypoglycemia on oxidative stress scavenger system and electron transport chain complexes from rat brain, liver, and kidney

Mol Chem Neuropathol

Severe hypoglycemia in adults

Rev Endocr Metab Disord

Diverse causes of hypoglycemia associated autonomic failure in diabetes

N Engl J Med

Mechanisms of sympathoadrenal failure and hypoglycemia in diabetes

J Clin Inv

Cellular Neuroscience
Research Paper
Selective vulnerability of brain regions to oxidative stress in a non-coma model of insulin-induced hypoglycemia