Background: Prolonged hypoglycemia leads to brain injury, despite treatment with 10% dextrose. Whether induction of hyperglycemia or ketonemia achieves better neuroprotection is unknown. Hyperglycemia is neuroprotective in other brain injuries during development; however, it worsens hypoglycemia-induced injury in the adult brain via poly(ADPribose)polymerase-1 (PARP-1) overactivation. Methods: Three-week-old rats were subjected to insulininduced hypoglycemia and treated with 10% dextrose or 50% dextrose. Neuronal injury, PARP-1, and brain-derived neurotrophic factor (BDNF) III/TrkB/p75 NTR expressions were determined. In the second experiment, ketonemia was induced by administering β-hydroxybutyrate during hypoglycemia and its effect on neuronal injury was compared with those conventionally treated using 10% dextrose. results: Both 10 and 50% dextrose administration led to hyperglycemia (50% dextrose > 10% dextrose). Compared with the 10% dextrose group, neuronal injury was greater in the 50% dextrose group and was accompanied by PARP-1 overactivation. BDNF III and p75 NTR , but not TrkB FL , mRNA expressions were upregulated. Neuronal injury was less severe in the rats subjected to ketonemia, compared with those conventionally treated using 10% dextrose. conclusion: Hyperglycemia accentuated hypoglycemiainduced neuronal injury, likely via PARP-1 overactivation. Although BDNF was upregulated, it was not neuroprotective and potentially exaggerated injury by binding to p75 NTR receptor. Conversely, ketonemia during hypoglycemia attenuated neuronal injury.
Background Hypoglycemia (HG) is common in IUGR neonates. In normally grown (NG) neonatal rats, acute HG causes neuronal injury in the brain, cerebral cortex more vulnerable than the hippocampus (HPC). We hypothesized that the IUGR brain is less vulnerable to hypoglycemia-induced injury while preserving the regional variation in vulnerability. Methods We induced IUGR via bilateral uterine artery ligation on gestational day 19 (term 22d) rats. On postnatal day 14, insulin-induced HG of equivalent severity and duration (blood glucose <40mg/dl for 240 min) was produced in IUGR and NG (IUGR/HG and NG/HG) groups. Neuronal injury in the cortex and HPC was quantified 6-72 hr later using Fluoro-Jade B (FJB) histochemistry. The mRNA expression of monocarboxylate transporters, MCT1 and MCT2, and glucose transporters, GLUT1, and GLUT3 was determined using qPCR. Results There were fewer FJB+ cells in the cortex of IUGR/HG; no difference was observed in FJB+ cells in HPC. Core body temperature was lower in IUGR/HG compared with NG/HG. MCT2 expression was increased in the IUGR cortex. Conclusion Hypoglycemia-induced neuronal injury is decreased in the cortex of the developing IUGR brain. Adaptations including systemic hypothermia and enhanced delivery of alternative substrates via MCT2 might protect against hypoglycemia-induced neuronal injury in IUGR.
A 5-month-old previously healthy term male infant presents to a rural emergency department (ED) for a 1-week history of increasing congestion, poor oral intake, and a temperature of 103°F (39.4°C). He is being treated with amoxicillin for presumed pneumonia. His examination in the ED is significant for scattered rhonchi and mild dehydration. His chest radiograph reveals inflammatory changes without a focal infiltrate (Fig 1). However, because this is his fourth presentation to the ED during this illness, he is admitted for observation. During the next 2 days his respiratory distress and tachypnea progressively worsen. On day 3 of his hospitalization he begins having episodes of desaturation and worsening retractions refractory to oxygen via low-flow nasal cannula. His examination at this time is significant for diffuse rhonchi throughout both lung fields with decreased air entry at the lung bases. Because his clinical status is deteriorating, he is transferred to a higher level of care. On arrival at the referral center he is lethargic, with decreased breath sounds and persistent desaturations. A respiratory swab polymerase chain reaction is positive for respiratory syncytial virus (RSV). His chest radiograph reveals a large right-sided tension pneumothorax (Fig 2). A pigtail chest tube is emergently placed, and his work of breathing improves. Within 2 days he is no longer requiring supplemental oxygen. The medical team is unable to successfully put the chest tube to water seal, however, because each time it is sealed there is a rapid re-accumulation of his pneumothorax. After several unsuccessful attempts, his chest tube is placed back to suction and he is airlifted, via helicopter, to a pediatric tertiary care center for further evaluation, now 11 days after his initial presentation. His chest radiograph just before transfer reveals a well-positioned chest tube with interval decrease in the size of the pneumothorax. On arrival at the tertiary care center he is well appearing, with no increased work of breathing, and is saturating 97% to 100% on room air. His lung sounds are clear bilaterally, but an air leak is auscultated on inspiration. He has no crackles, wheezes, or rhonchi. Chest radiography is repeated to verify the position of the chest tube and incidentally reveals a large cystic-appearing lesion in his right lung that has not been previously described (Fig 3). Computed tomography of the chest is performed that reveals multiple air-filled cystic lesions in the right upper lobe of the lung as well as a persistent right-sided pneumothorax (Fig 4). Surgery and pulmonology are consulted for co-management. On day 17 of his cumulative hospitalization he undergoes wedge resection of the right upper lobe of his lung without complications. Samples of the cystic lesions are sent to the pathology laboratory to confirm the diagnosis. AUTHOR DISCLOSURE Drs Stein, Molero, Hess, Luquette, and Pitt have disclosed no financial relationships relevant to this article. This commentary does not contain a discussion of an un...
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