title: Recurrent hypoinsulinemic hyperglycemia in neonatal rats increases PARP-1 and NF-κB expression and leads to microglial activation in the cerebral cortex.
abstract: BACKGROUND
  Hyperglycemia is a common metabolic problem in extremely low-birth-weight preterm infants. Neonatal hyperglycemia is associated with increased mortality and brain injury. Glucose-mediated oxidative injury may be responsible. Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear enzyme involved in DNA repair and cell survival. However, PARP-1 overactivation leads to cell death. NF-κB is coactivated with PARP-1 and regulates microglial activation. The effects of recurrent hyperglycemia on PARP-1/NF-κB expression and microglial activation are not well understood.
  
  
  METHODS
  Rat pups were subjected to recurrent hypoinsulinemic hyperglycemia of 2 h duration twice daily from postnatal (P) day 3-P12 and killed on P13. mRNA and protein expression of PARP-1/NF-κB and their downstream effectors were determined in the cerebral cortex. Microgliosis was determined using CD11 immunohistochemistry.
  
  
  RESULTS
  Recurrent hyperglycemia increased PARP-1 expression confined to the nucleus and without causing PARP-1 overactivation and cell death. NF-κB mRNA expression was increased, while IκB mRNA expression was decreased. inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS), and neuronal nitric oxide synthase (nNOS) mRNA expressions were decreased. Hyperglycemia significantly increased the number of microglia.
  
  
  CONCLUSIONS
  Recurrent hyperglycemia in neonatal rats is associated with upregulation of PARP-1 and NF-κB expression and subsequent microgliosis but not neuronal cell death in the cerebral cortex.
authors.affiliation: Division of Neonatology, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Tate
authors.initials: T
authors.lastname: Gisslen
authors.affiliation: Division of Neonatology, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Ennis
authors.affiliation: Department of Pediatrics (Neonatology) and Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut.|Current address: Department of Pediatrics, Division of Neonatology, St. Christopher's Hospital for Children, Drexel University, Philadelphia, Pennsylvania.
authors.forename: Vineet
authors.initials: V
authors.lastname: Bhandari
authors.affiliation: Division of Neonatology, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Raghavendra
authors.initials: R
authors.lastname: Rao
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001786:Blood Glucose / Q000378:metabolism; D018845:CD11 Antigens / Q000378:metabolism; D002540:Cerebral Cortex / Q000201:enzymology* / Q000473:pathology; D004195:Disease Models, Animal; D005947:Glucose; D006943:Hyperglycemia / Q000097:blood / Q000139:chemically induced / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism; D007328:Insulin / Q000097:blood*; D017628:Microglia / Q000201:enzymology* / Q000473:pathology; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D015282:Octreotide; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D012008:Recurrence; D015398:Signal Transduction; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D001786:Blood Glucose; D018845:CD11 Antigens; D020672:I-kappa B Proteins; D007328:Insulin; D016328:NF-kappa B; C000606206:Nfkbia protein, rat; D012333:RNA, Messenger; D000072000:NF-KappaB Inhibitor alpha; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat; C499322:Parp1 protein, rat; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D005947:Glucose; D015282:Octreotide