Acute hypoglycemia is associated with neuronal injury in the mature human and rodent brains. Even though hypoglycemia is a common metabolic problem during development, its effects on the developing brain are not well understood. To characterize the severity of regional brain injury, postnatal day (P) 7, P14, P28 (N=20-30/age) and adult rats (N=8-12) were subjected to acute hypoglycemia of equivalent severity and duration (mean blood glucose concentration: 30.0±0.1 mg/ dL for 210 min). Neuronal injury in the cerebral cortex, striatum, hippocampus and hypothalamus was assessed 24 hr, 72 hr and 1 wk later by determining the number of degenerating cells positive for Fluoro-Jade B (FJB+) in the region. Compared with age-matched control, greater number of FJB + cells was present per brain section of P14, P28 and adult hypoglycemia groups (P<0.005, each). The cerebral cortex was more vulnerable than hippocampus and striatum at all three ages (P<0.01). Compared with P28 (131±21) and adult (171±21) rats, fewer FJB+ cells (39±6) per brain section were present in P14 hypoglycemic rats (P<0.01, each). Hypoglycemia was not associated with cell injury in P7 rats. FJB+ cells were absent in the hypothalamus in all four ages. Similar results were present 24 hr post-hypoglycemia, where as analysis at 1 wk demonstrated efficient clearing of FJB + cells in the brain regions of developing rats. Varying the duration of fasting did not alter the severity of regional cell injury. These results suggest that postnatal age influences the regional vulnerability to hypoglycemia-induced neuronal death in the rat brain.

The cognitive deficits observed in children with cyanotic congenital heart disease suggest involvement of the developing hippocampus. Chronic postnatal hypoxia present during infancy in these children may play a role in these impairments. To understand the biochemical mechanisms of hippocampal injury in chronic hypoxia, a neurochemical profile consisting of 15 metabolite concentrations and 2 metabolite ratios in the hippocampus was evaluated in a rat model of chronic postnatal hypoxia using in vivo 1 H NMR spectroscopy at 9.4 T. Chronic hypoxia was induced by continuously exposing rats (n = 23) to 10% O 2 from postnatal day (P) 3 to P28. Fifteen metabolites were quantified from a volume of 9-11 Al centered on the left hippocampus on P14, P21, and P28 and were compared with normoxic controls (n = 14). The developmental trajectory of neurochemicals in chronic hypoxia was similar to that seen in normoxia. However, chronic hypoxia had an effect on the concentrations of the following neurochemicals: aspartate, creatine, phosphocreatine, GABA, glutamate, glutamine, glutathione, myoinositol, N-acetylaspartate (NAA), phosphorylethanolamine, and phosphocreatine/creatine (PCr/Cr) and glutamate/glutamine (Glu/Gln) ratios ( P b 0.001 each, except glutamate, P = 0.04). The increased PCr/Cr ratio is consistent with decreased brain energy consumption. Given the well-established link between excitatory neurotransmission and brain energy metabolism, we postulate that elevated glutamate, Glu/Gln ratio, and GABA indicate suppressed excitatory neurotransmission in an energy-limited environment. Decreased NAA and phosphorylethanolamine suggest reduced neuronal integrity and phospholipid metabolism. The altered hippocampal neurochemistry during its development may underlie some of the cognitive deficits present in human infants at risk of chronic hypoxia. D 2005 Elsevier B.V. All rights reserved.Theme: Other systems of the CNS Topic: Brain metabolism and blood flow

This report reviews laryngoplastic techniques for correction of bowing of the vocal cords, with special consideration to the anatomic details of the anterior commissure. I present a new technique in which the glottic gap is closed by bilateral medialization. This technique may be superior to those described previously, since the correction achieved at the time of surgery is maintained by the placement of Silastic

BackgroundHyperglycemia is common in extremely low gestational age newborns (ELGAN) and is associated with increased mortality and morbidity, including abnormal neurodevelopment. Hippocampus-mediated cognitive deficits are common in this population, but the specific effects of hyperglycemia on the developing hippocampus are not known.MethodsThe objective of this study was to determine the acute and long-term effects of hyperglycemia on the developing hippocampus in neonatal rats using a streptozotocin (STZ)-induced model of hyperglycemia. STZ was injected on postnatal day (P) 2, and littermates in the control group were injected with an equivalent volume of citrate buffer. The acute effects of hyperglycemia on markers of oxidative stress, inflammatory cytokines, microglial activation, and reactive astrocytosis in the hippocampus were determined in the brain tissue collected on P6. The long-term effects on hippocampus-mediated behavior and hippocampal dendrite structure were determined on P90.ResultsOn P6, the transcript and protein expression of markers of oxidative stress and inflammatory cytokines, including the CXCL10/CXCR3 pathway, were upregulated in the hyperglycemia group. Histological evaluation revealed microglial activation and astrocytosis. The long-term assessment on P90 demonstrated abnormal performance in Barnes maze neurobehavioral testing and altered dendrite structure in the hippocampus of formerly hyperglycemic rats.ConclusionsNeonatal hyperglycemia induces CXCL10/CXCR3 signaling, microglial activation, and astrocytosis in the rat hippocampus and alters long-term synaptogenesis and behavior. These results may explain the hippocampus-specific cognitive deficits common in ELGAN who experience neonatal hyperglycemia.

Poly(ADP-ribose) polymerase-1 (PARP-1) overactivation plays a significant role in hypoglycemia-induced brain injury in adult rats. To determine the influence of postnatal age on PARP-1 activation, developing and adult male rats were subjected to acute hypoglycemia of equivalent severity and duration. The expression of PARP-1 and its downstream effectors, apoptosis-inducing factor (Aifm1), caspase 3 (Casp3), NF-B (Nfkb1) and bcl-2 (Bcl2), and cellular poly(ADP-ribose) (PAR) polymer expression were assessed in the cerebral cortex, hippocampus, striatum, and hypothalamus at 0 h and 24 h posthypoglycemia. Compared with the control group, PARP-1 expression increased in the cerebral cortex of adult rats 24 h posthypoglycemia, but not at 0 h, and it was accompanied by increased number of PAR-positive cells. The expression was not altered in other brain regions. Aifm1, Nfkb1, Casp3, and Bcl2 expressions also increased in the cerebral cortex of adult rats 24 h posthypoglycemia. Conversely, hypoglycemia did not alter PARP-1 expression and its downstream effectors in any brain region in developing rats. These data parallel the previously demonstrated pattern of hypoglycemia-induced brain injury and suggest that PARP-1 overactivation may determine age-and region-specific vulnerability during hypoglycemia. We have recently demonstrated that the developing brain is less vulnerable than the mature brain to injury during moderate hypoglycemia in rats (2). Compared with the adult rats, neuronal injury was 4-fold less severe in postnatal day (P) 14 (i.e., developing) rats (2). This study and previous studies have also demonstrated that neuronal injury is primarily confined to the cerebral cortex in moderate hypoglycemia (2-4). The factors responsible for the age-and region-specific vulnerability are not well understood.Activation of poly(ADP-ribose) polymerase-1 (PARP-1) is an important component of hypoglycemia-induced neuronal injury in adult rats (5). PARP-1 is a nuclear enzyme responsible for maintaining the genomic integrity and chromatin structure under basal conditions (6 -9). On activation by DNA strand breaks, PARP-1 catalyzes the formation of poly(ADPribose) (PAR) polymers that bind to acceptor proteins near the site of DNA damage and facilitate its repair (reviewed in Refs. 7,8). However, PARP-1 overactivation leads to cell death by depletion of cellular NAD ϩ