Effect of Insulin-Induced and Fasting Hypoglycemia on Perinatal Hypoxic-Ischemic Brain Damage

Yager, Jerome Y.; Heitjan, Daniel F.; Towfighi, Javad; Vannucci, Robert C.

doi:10.1203/00006450-199202000-00009

Cited by 123 publications

(49 citation statements)

References 32 publications

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“…In a forebrain ischemia model in adult rats preloaded with glucose, postischemic treatment with low-dose insulin reduced mortality and the incidence of postischemic seizures (1 1). However, a recent study in neonatal rat showed an increase in mortality when animals were insulin-treated before induction of hypoxia-ischemia (20). Juvenile monkeys who received infusions of glucose just before cardiac arrest showed widespread cortical and basal ganglia necrosis (8).…”

Section: Discussionmentioning

confidence: 99%

Postischemic Hyperglycemia Is Not Protective to the Neonatal Rat Brain

1992

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ABSTRACT. Brain glucose concentration during and after hypoxia-ischemia may be one of the variables affecting outcome of asphyxia1 insults. Glucose given before global ischemic forebrain iniurv to adult rats increases morehologic brain damage, i n d postischemic insulin administration reduces selective neuronal necrosis and cortical infarction. Because glucose infusions are routinely used in the clinical management of perinatal asphyxia, we evaluated the role of slucose administration after ischemic neuronal damage to neonatal rat brain. Sprague-Dawley rat pups (postnatal d 7) were subjected to left common carotid artery ligation followed by 2.5 h of 8% oxygen (Levine procedure). The experimental group was subdivided so that pups received either systemic injections of glucose or saline immediately after the hypoxic insult. Animals were killed on postnatal d 12 and brain areas of ipsi-and contralateral cortex and caudate were calculated from camera lucida tracings. There was no significant difference in size of brain infarction between postischemic glucose-treated and postischemic saline-treated pups. However, hypoxic-ischemic brains did show more severe neuronal damage when hyperglycemia was induced after asphyxia. Because postischemic hyperglycemia does not attenuate and may exacerbate injury, we recommend careful monitoring of blood glucose so that hyperglycemia does not occur during resuscitation of asphyxiated infants. (Pediatr Res 32: 489-493, 1992) Abbreviations NADPH-d, NADPH diaphorase EAA, excitatory amino acidNeurologic morbidity occurs in 20-30% of infants suffering acute perinatal asphyxia in the United States (I). The hypoxicischemic encepha~opath~ seen in survivors of pennatal asphyxia is a commonly encountered clinical problem and is thought to be the largest contributor to static encephalopathies in infants and children (2). Hypoglycemia is a frequent metabolic derangement among asphyxiated infants and has additive deleterious effects on the CNS sequelae of perinatal asphyxia (3-5). Standard resuscitation procedures use glucose infusions to correct posthypoxic hypoglycemia, but this procedure often results in hyperglycemia (6).

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Section: Discussionmentioning

confidence: 99%

Postischemic Hyperglycemia Is Not Protective to the Neonatal Rat Brain

1992

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“…38 Noncirculatory factors contributing to neuronal preservation Additional factors considered potentially important in preserving neuronal integrity with asphyxia include biologic alterations that are maturation dependent. Some examples include: (1) decreasing rate of brain metabolism during early development that results in a slower depletion of high-energy compounds during hypoxiaischemia in the fetus as compared with the term infant or adult; 39,40 (2) the use of alternate energy substrate, the neonatal brain having the capacity to use lactate and ketone bodies for energy production; 41,42 (3) the relative resistance of the fetal and neonatal myocardium to hypoxia ischemia; 43,44 and (4) the potential protective role of fetal hemoglobin, that is, it has been calculated that if the PO 2 were to decrease to below a value of approximately 3 torr, and if the venous PO 2 were to decrease to 10 torr (a value that may be found in the cerebral venous blood with asphyxia), the infant would have more oxygen available for brain uptake with a fetal rather than with an adult dissociation curve. 45 Recent data suggest a potential important role for ischemic preconditioning.…”

Section: Circulatory Responsesmentioning

confidence: 99%

Pathogenesis of hypoxic-ischemic brain injury

Perlman

2007

J Perinatol

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Accumulating evidence points to an evolving process of brain injury after intrapartum hypoxia-ischemia that initiates in utero and extends into a recovery period. The processes leading to cell death include necrosis or apoptosis, and result from the combined effects of cellular energy failure, acidosis, glutamate release, intracellular Ca 2 þ accumulation, generation of free radicals that serve to disrupt essential components of the cell. Many factors including the duration or severity of the insult influence the progression of cellular injury after hypoxia-ischemia. A secondary cerebral energy failure occurs from 6 to 48 h after the primary event and involves mitochondrial dysfunction secondary to extended reactions from primary insults (e.g., calcium influx, excitatory neurotoxicity and oxygen free radicals) as well as the release of circulatory and endogenous inflammatory cells/mediators that also contribute to ongoing brain injury. Strategies aimed at neuroprotection need to be comprehensive targeting the pathways leading to eventual mitochondrial injury.

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“…Evaluation of the presence and extent of chronic gross morphologic and microscopic alterations was performed by two investigators, each blinded to group assignment. For gross examination, the type and extent of changes such as atrophy and cavitation were noted, as previously described (18,19). The severity of damage within each brain was grossly scored as follows.…”

Section: Neuropathologic Analysismentioning

confidence: 99%