Brain contains a highly diversified complement of molecular species of a mitochondria-specific phospholipid, cardiolipin (CL), which - due to its polyunsaturation - can readily undergo oxygenation. Here, we used global lipidomics analysis in experimental traumatic brain injury (TBI) and showed that TBI was accompanied by oxidative consumption of polyunsaturated CL and accumulation of more than 150 new oxygenated molecular species in CL. RNAi-based manipulations of CL-synthase and CL levels conferred resistance of primary rat cortical neurons to mechanical stretch - an in vitro model of traumatic neuronal injury. By applying the novel brain permeable mitochondria-targeted electron-scavenger, we prevented CL oxygenation in the brain, achieved a substantial reduction in neuronal death both in vitro and in vivo, and markedly reduced behavioral deficits and cortical lesion volume. We conclude that CL oxygenation generates neuronal death signals and that its prevention by mitochondria-targeted small molecule inhibitors represents a new target for neuro-drug discovery.

ABSTRACT. Objectives. To assess the incidence and complications of breastfeeding-associated hypernatremic dehydration among hospitalized neonates.Study Design. A retrospective study was conducted at Children's Hospital of Pittsburgh over a 5-year period, to identify otherwise healthy term and near-term (>35 weeks of gestation) breastfed neonates (<29 days of age) who were admitted with serum sodium concentrations of >150 mEq/L and no explanation for hypernatremia other than inadequate milk intake.Results. The incidence of breastfeeding-associated hypernatremic dehydration among 3718 consecutive term and near-term hospitalized neonates was 1.9%, occurring for 70 infants. These infants were born primarily to primiparous women (87%) who were discharged within 48 hours after birth (90%). The most common presenting symptom was jaundice (81%). Sixty-three percent of infants underwent sepsis evaluations with lumbar puncture. No infants had bacteremia or meningitis. Infants had hypernatremia of moderate severity (median: 153 mEq/L; range: 150 -177 mEq/L), with a mean weight loss of 13.7%. Nonmetabolic complications occurred for 17% of infants, with the most common being apnea and/or bradycardia. There were no deaths. Diseases, Ninth Revision, Clinical Modification; MWH, Magee-Womens Hospital. T he benefits of breastfeeding to children are well established and include decreased incidence of a wide variety of acute infections and chronic diseases, as well as improved neurodevelopmental outcomes. 1,2 A serious potential complication of insufficient breastfeeding is severe hypernatremic dehydration. 3 Neonatal hypernatremic dehydration results from inadequate transfer of breast milk from mother to infant. Furthermore, poor milk drainage from the breasts results in persistence of high milk sodium concentrations. 4 This may exacerbate neonatal hypernatremia. 5,6 We refer to this as "breastfeeding-associated hypernatremia," with the clear understanding that this results only when breastfeeding is not properly established. Hypernatremic dehydration is assumed to be a rare complication of breastfeeding, 7 but recent reports have suggested that the incidence is increasing. [8][9][10][11] The failure to diagnose hypernatremic dehydration can have serious consequences, including seizures, intracranial hemorrhage, 12 vascular thrombosis, 13 and death. 14,15 The purpose of this study was to assess the incidence and complications of breastfeeding-associated hypernatremia among hospitalized neonates at a large pediatric tertiary care center in the United States. Conclusion. Hypernatremic dehydration requiring ABBREVIATIONS. ICD-9-CM, International Classification of METHODSChildren's Hospital of Pittsburgh is a 235-bed freestanding hospital with ϳ12 000 admissions per year. After approval was obtained from the institutional review board, a retrospective study was conducted to identify otherwise healthy term and near-term (gestation of Ն35 weeks) neonates admitted during a 5-year period with serum sodium concentrations of Ն150 mEq/L...

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