Effects of Exogenous Glucose on Brain Ischemia in Ovine Fetuses

Petersson, Katherine H.; Pınar, Halit; Stopa, Edward G.; Sadowska, Grazyna B.; Hanumara, R. Choudary; Stonestreet, Barbara S.

doi:10.1203/01.pdr.0000139415.96985.bf

Cited by 20 publications

(18 citation statements)

References 62 publications

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“…In contrast, post-insult treatment has had variable results. Some studies, in neonatal rodents, piglets and fetal sheep, have suggested no effect 16 33 34. In contrast, in newborn piglets, hyperglycaemia impaired recovery of brain cell membrane function and energy metabolism 35.…”

Section: Discussionmentioning

confidence: 99%

Hypoglycaemia and hyperglycaemia are associated with unfavourable outcome in infants with hypoxic ischaemic encephalopathy: a post hoc analysis of the CoolCap Study

Basu

Kaiser

Guffey

et al. 2015

Arch Dis Child Fetal Neonatal Ed

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Section: Discussionmentioning

confidence: 99%

Hypoglycaemia and hyperglycaemia are associated with unfavourable outcome in infants with hypoxic ischaemic encephalopathy: a post hoc analysis of the CoolCap Study

Basu

Kaiser

Guffey

et al. 2015

Arch Dis Child Fetal Neonatal Ed

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“…Alternatively, glucose may serve as marker for fetal adaptive responses to hypoxia that are protective by alternative mechanisms. The role of glucose in modulation of damage during H-I in young fetuses remains unclear [54]. Future in vitro and in vivo studies are needed to analyze the potential of glucose supplementation to mitigate WMI.…”

Section: Discussionmentioning

confidence: 99%

Hemodynamic and Metabolic Correlates of Perinatal White Matter Injury Severity

et al. 2013

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Background and PurposeAlthough the spectrum of perinatal white matter injury (WMI) in preterm infants is shifting from cystic encephalomalacia to milder forms of WMI, the factors that contribute to this changing spectrum are unclear. We hypothesized that the variability in WMI quantified by immunohistochemical markers of inflammation could be correlated with the severity of impaired blood oxygen, glucose and lactate.MethodsWe employed a preterm fetal sheep model of in utero moderate hypoxemia and global severe but not complete cerebral ischemia that reproduces the spectrum of human WMI. Since there is small but measurable residual brain blood flow during occlusion, we sought to determine if the metabolic state of the residual arterial blood was associated with severity of WMI. Near the conclusion of hypoxia-ischemia, we recorded cephalic arterial blood pressure, blood oxygen, glucose and lactate levels. To define the spectrum of WMI, an ordinal WMI rating scale was compared against an unbiased quantitative image analysis protocol that provided continuous histo-pathological outcome measures for astrogliosis and microgliosis derived from the entire white matter. ResultsA spectrum of WMI was observed that ranged from diffuse non-necrotic lesions to more severe injury that comprised discrete foci of microscopic or macroscopic necrosis. Residual arterial pressure, oxygen content and blood glucose displayed a significant inverse association with WMI and lactate concentrations were directly related. Elevated glucose levels were the most significantly associated with less severe WMI.ConclusionsOur results suggest that under conditions of hypoxemia and severe cephalic hypotension, WMI severity measured using unbiased immunohistochemical measurements correlated with several physiologic parameters, including glucose, which may be a useful marker of fetal response to hypoxia or provide protection against energy failure and more severe WMI.

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“…Studies in neonatal mouse [66] and rat [67,68] models of hypoxic and/or ischemic encephalopathy show benefi t to glucose supplementation and worse survival with insulin-induced hypoglycemia [69] . In contrast, hypoxic and/or ischemic brain damage in newborn piglets and fetal sheep is made worse by hyperglycemia and improved with insulin-induced hypoglycemia [70,71] , although in another study in newborn sheep, cerebral oxygen consumption was maintained better with experimental hyperglycemia than insulin-induced hypoglycemia or in control animals following an 'asphyxial' (hypoxic-ischemic) episode [72] . Based on the above confl icting fi ndings, normalizing glucose concentration in the circulation of infants with severe acidosis who are at risk for developing hypoxic-ischemic encephalopathy is a reasonable goal.…”

Section: The Infant With Hypoxic-ischemic Encephalopathymentioning

confidence: 97%

Hypoglycemia in Newborn Infants: Features Associated with Adverse Outcomes

2006

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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.

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Effects of Exogenous Glucose on Brain Ischemia in Ovine Fetuses

Cited by 20 publications

References 62 publications

Hypoglycaemia and hyperglycaemia are associated with unfavourable outcome in infants with hypoxic ischaemic encephalopathy: a post hoc analysis of the CoolCap Study

Hypoglycaemia and hyperglycaemia are associated with unfavourable outcome in infants with hypoxic ischaemic encephalopathy: a post hoc analysis of the CoolCap Study

Hemodynamic and Metabolic Correlates of Perinatal White Matter Injury Severity

Hypoglycemia in Newborn Infants: Features Associated with Adverse Outcomes

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