Combination of Systemic Hypothermia and N-acetylcysteine Attenuates Hypoxic-Ischemic Brain Injury in Neonatal Rats
- 1 May 2006
- journal article
- Published by Springer Nature in Pediatric Research
- Vol. 59 (5) , 684-689
- https://doi.org/10.1203/01.pdr.0000215045.91122.44
Abstract
Hypoxic ischemic (HI) injury in neonates may have devastating, long-term consequences. Recently completed clinical trials in HI neonates indicate that hypothermia within 6 h of birth results in modest improvement in the combined outcome of death or severe disability. The aim of this study was to investigate the effects of combining hypothermia and N-acetylcysteine (NAC) on brain injury, neonatal reflexes and myelination after neonatal HI. Seven-day-old rats were subjected to right common carotid artery ligation and hypoxia (8% oxygen) for 2 h. Systemic hypothermia (30 + 0.5°C) was induced immediately after the period of HI and was maintained for 2 h. NAC (50 mg/kg) was administered by intraperitoneal injection daily until sacrifice. Brain infarct volumes were significantly reduced at 48 h post-HI in the hypothermia plus NAC group (21.5 ± 3.84 mm3) compared with vehicle (240.85 ± 4.08 mm3). Neonatal reflexes were also significantly improved by combination therapy at days 1 and 7. There was a significant loss of right hemispheric brain volume in the untreated group at 2 and 4 wk after HI insult. Brain volumes were preserved in hypothermia plus NAC group and were not significantly different when compared with the sham group. Similarly, increased myelin expression was seen in brain sections from hypothermia plus NAC group, when stained for Luxol Fast Blue (LFB), Myelin Basic Protein (MBP) and Proteolipid protein (PLP). These results indicate that hypothermia plus NAC combination therapy improves infarct volume, myelin expression and functional outcomes after focal HI injury.Keywords
This publication has 32 references indexed in Scilit:
- Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trialPublished by Elsevier ,2005
- Moderate hypothermia in neonatal encephalopathy: Safety outcomesPediatric Neurology, 2005
- Moderate hypothermia in neonatal encephalopathy: Efficacy outcomesPediatric Neurology, 2005
- Long-Term Neurodevelopmental Outcome of Asphyxiated NewbornsClinics in Perinatology, 1999
- Modest Hypothermia Provides Partial Neuroprotection when Used for Immediate Resuscitation after Brain IschemiaPediatric Research, 1997
- Dramatic neuronal rescue with prolonged selective head cooling after ischemia in fetal lambs.Journal of Clinical Investigation, 1997
- Effect of Mild Hypothermia on Cerebral Energy Metabolism During the Evolution of Hypoxic-Ischemic Brain Damage in the Immature RatStroke, 1996
- Delayed and prolonged post-ischemic hypothermia is neuroprotective in the gerbilBrain Research, 1994
- Acute neonatal morbidity and long-term central nervous system sequelae of perinatal asphyxia in term infantsEarly Human Development, 1991
- COMPARISON OF TWO METHODS OF PREDICTING OUTCOME IN PERINATAL ASPHYXIAThe Lancet, 1986