Alterations in Cerebral Mitochondria during Acute Hypoglycemia

Ballesteros, Juan R.; Mishra, Om P.; McGowan, Jane E.

doi:10.1159/000071951

Cited by 28 publications

(11 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…28 Subsequent work also shows neuronal hypoglycemia induces marked increases in both mitochondrial superoxide and hydrogen peroxide production. 29, 30 Further work using inhibitors of the mitochondrial ETC and measurements of specific activity levels of components of the ETC will be necessary to determine the exact ETC sources of mitochondrial ROS under low glucose conditions.…”

Section: Discussionmentioning

confidence: 99%

Acute Exposure to Low Glucose Rapidly Induces Endothelial Dysfunction and Mitochondrial Oxidative Stress

Wang

Alexanian

Rong

et al. 2012

ATVB

119

114

View full text Add to dashboard Cite

Objective Hypoglycemia is associated with increased mortality. The reasons for this remain unclear and the effects of low glucose exposure on vascular endothelial function remain largely unknown. We endeavored to determine the effects of low glucose on endothelial cells and intact human arterioles. Methods and Results We exposed human umbilical vein endothelial cells to low glucose conditions in a clinically relevant range (40–70 mg/dL) and found rapid and marked reductions in nitric oxide (NO) bioavailability (P<0.001). This was associated with concomitantly increased mitochondrial superoxide production (P<0.001) and NO-dependent mitochondrial hyperpolarization (P<0.001). Reduced NO bioavailability was rapid and attributable to reduced eNOS activity and destruction of NO. Low glucose rapidly activated AMP Kinase but physiological activation failed to restore NO bioavailability. Pharmacological AMP Kinase activation led to phosphorylation of eNOS’s Ser633 activation site, reversing the adverse effects of low glucose, and this protective effect was prevented by L-NAME. Intact human arterioles exposed to low glucose demonstrated marked endothelial dysfunction which was prevented by either metformin or TEMPOL. Conclusions Our data suggest that moderate low glucose exposure rapidly impairs NO bioavailability and endothelial function in the human endothelium, and that pharmacological AMP Kinase activation can inhibit this effect in an NO-dependent manner.

show abstract

Section: Discussionmentioning

confidence: 99%

Acute Exposure to Low Glucose Rapidly Induces Endothelial Dysfunction and Mitochondrial Oxidative Stress

Wang

Alexanian

Rong

et al. 2012

ATVB

119

114

View full text Add to dashboard Cite

show abstract

“…In addition to the increased free radical generation, a 50-60% decrease in brain ATP and phosphocreatine levels has been demonstrated in the newborn piglet model of hypoglycemia used to test this hypothesis [55] . These studies were done with the piglet under general anesthesia.…”

Section: Mechanism Of Injurymentioning

confidence: 99%

Hypoglycemia in Newborn Infants: Features Associated with Adverse Outcomes

2006

View full text Add to dashboard Cite

The purpose of this review article is to document from the literature values of blood/plasma glucose concentration and associated clinical signs and conditions in newborn infants (both term and preterm) that indicate a reasonable clinical probability that hypoglycemia is a proximate cause of acute and/or sustained neurological injury and to review the physiological and pathophysiological responses to hypoglycemia that may influence the ultimate outcome of newborns with low blood glucose. Our overall conclusion is that there is inadequate information in the literature to define any one value of glucose below which irreparable hypoglycemic injury to the central nervous system occurs, at any one time or for any defined period of time, in a population of infants or in any given infant. Clinical signs of prolonged and severe neurological disturbance (coma, seizures), extremely and persistently low plasma/blood glucose concentrations (0 to <1.0 mmol/l [0 to <18–20 mg/dl] for more than 1–2 h), and the absence of other obvious central nervous system (CNS) pathology (hypoxia-ischemia, intracranial hemorrhage, infection, etc.) are important for the diagnosis of injury due to glucose deficiency. Specific conditions, such as persistent hyperinsulinemia with severe hypoglycemic episodes that include seizures, also contribute to the diagnosis of hypoglycemic injury. Such lack of definitive measures of injury specific to glucose deficiency indicates that clinicians should be on the alert for infants at risk of hypoglycemia and for clinical signs and conditions that might herald severe hypoglycemia; they should have a low threshold for investigating and diagnosing ‘hypoglycemia’ with frequent measurements of plasma/blood glucose concentration; and they should treat low glucose concentrations promptly and maintain them in a safe range. Because there is no conclusive evidence or consensus in the literature that defines an absolute value or duration of ‘hypoglycemia’ that must occur, with our without related clinical complications, to produce neurological injury, clinicians should consider the information currently available, determine a ‘target’ plasma or blood glucose concentration that is acceptable, and treat infants with glucose concentrations below this value accordingly. Our intent in this review article is to highlight the studies relevant to this issue and help clinicians formulate a safe and, hopefully, effective strategy for the diagnosis and treatment of hypoglycemia.

show abstract

“…However, few large systematic studies have been conducted to characterize the association of neonatal hypoglycemic brain injury with infantile spasms. The lack of glucose can selectively impair multiple brain regions, including the superficial cortex, dentate gyrus, hippocampus, and caudate putamen; this impairment occurs through several putative mechanisms, such as the release of excitatory neurotransmitter (19), increased mitochondrial free radical generation and initiation of apoptosis (20), activation of neuronal nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (21), and altered cerebral energetic characteristics (22,23). In one study in which the etiology of remote symptomatic epilepsy with onset during the first 3 years of life was examined, it was observed that neonatal hypoglycemia was the most common etiology, and infantile spasms were the most common type of seizure (14).…”

Section: Discussionmentioning

confidence: 99%

Neonatal hypoglycemic brain injury is a cause of infantile spasms

Yang

Zou

Wang

et al. 2016

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

Abstract. Neonatal hypoglycemic brain injury is one of the causes of infantile spasms. In the present study, the clinical history and auxiliary examination results of 18 patients who developed infantile spasms several months after neonatal hypoglycemia were retrospectively analyzed. Among the 666 patients with infantile spasms admitted to two pediatric centers between January 2008 and October 2012, 18 patients developed infantile spasms after being diagnosed with neonatal hypoglycemia, defined as a whole blood glucose concentration of <2.6 mmol/l. These patients developed infantile spasms from between 2 and 10 months (mean, 4.9 months) following the diagnosis of neonatal hypoglycemia. All 18 patients had abnormal electroencephalographic findings with either classical or modified hypsarrhythmia. Upon examination using brain magnetic resonance imaging (MRI), 10 patients (55.6%) exhibited abnormalities. The MRI results principally showed a disproportional involvement of parietal and occipital cortices and sub-cortical white matter lesions. In conclusion, the results of this study indicate that neonatal hypoglycemic brain injury is associated with the subsequent development of infantile spasms.

show abstract

Alterations in Cerebral Mitochondria during Acute Hypoglycemia

Cited by 28 publications

References 34 publications

Acute Exposure to Low Glucose Rapidly Induces Endothelial Dysfunction and Mitochondrial Oxidative Stress

Acute Exposure to Low Glucose Rapidly Induces Endothelial Dysfunction and Mitochondrial Oxidative Stress

Hypoglycemia in Newborn Infants: Features Associated with Adverse Outcomes

Neonatal hypoglycemic brain injury is a cause of infantile spasms

Contact Info

Product

Resources

About