Clinical NeuroscienceResearch PaperSeizures are associated with brain injury severity in a neonatal model of hypoxia–ischemia
Section snippets
Animals
Large White newborn piglets (n=42) were obtained from the University of Queensland Gatton Piggery. Average age and weight was 17.0 h (±1.3) and 1.47 kg (±0.03) respectively. Approval for this study was obtained from the University of Queensland Animal Experimentation Ethics Committee and was carried out in accordance with National Health and Medical Research Council guidelines (Australia). Care was taken to minimize the number of animals used and to ensure no undue pain or distress.
Hypoxia/ischemia
The H/I
Results
Thirty-eight animals received H/I. Ten animals developed clinical seizures that were unresponsive to anticonvulsant treatment and in accordance with University of Queensland Animal Ethics were euthanased prior to the 72 h endpoint; these animals were excluded from further analysis consistent with our aim (to study survivable H/I brain injury and seizures) as complete EEG, clinical seizure and MRI/1H-MRS data were not available. The surviving H/I animals (n=28) were grouped for statistical
Discussion
In this study we demonstrate that seizures are associated with increasing severity of brain injury following a global H/I insult in the neonatal term piglet. Whilst damage was apparent in all H/I animals as determined from in vivo measures and neuropathology, the greatest degree of brain injury was observed in animals with seizures compared to animals in which seizure activity was absent. In our model 75% of all H/I animals developed seizures post-insult which we observed as clinical seizures
Acknowledgments
We wish to thank LED Wallis and NJ Stevenson for assistance with experiments and analysis. Financial support was provided by The National Health and Medical Research Council (Australia) (grant ID: 351501).
References (42)
- et al.
Hypoxic/Ischemic models in newborn piglet: comparison of constant FiO2 versus variable FiO2 delivery
Brain Res
(2006) Prolonged electroencephalogram monitoring for seizures and their treatment
Clin Perinatol
(2006)- et al.
Comparative aspects of the brain growth spurt
Early Hum Dev
(1979) - et al.
An improved survival model of hypoxia/ischaemia in the piglet suitable for neuroprotection studies
Brain Res
(2001) - et al.
Clinical neonatal seizures are independently associated with outcome in infants at risk for hypoxic-ischemic brain injury
J Pediatr
(2009) - et al.
Seizures in the developing brain: perhaps not so benign after all
Neuron
(1998) - et al.
Increased cerebral lactate during hypoxia may be neuroprotective in newborn piglets with intrauterine growth restriction
Brain Res
(2007) - et al.
Early serial EEG in hypoxic ischaemic encephalopathy
Clin Neurophysiol
(2001) - et al.
Improved method for accurate and efficient quantification of MRS data with use of prior knowledge
J Magn Reson
(1997) Neonatal seizures: to treat or not to treat?
Semin Pediatr Neurol
(2005)
Neonatal seizures
Pediatr Clin North Am
Intrapartum risk factors for newborn encephalopathy: the Western Australian case-control study
BMJ
Antiepileptic drugs and apoptosis in the developing brain
Ann N Y Acad Sci
Outcome of electroclinical, electrographic, and clinical seizures in the newborn infant
Dev Med Child Neurol
Recurrent seizures in the developing brain are not harmful
Epilepsia
Early diffusion weighted imaging and expression of heat shock protein 70 in newborn pigs with hypoxic ischaemic encephalopathy
Postgrad Med J
The exact ictal and interictal duration of electroencephalographic neonatal seizures
Epilepsia
Occult neonatal seizures
Epilepsia
Fisch and Spehlmann's EEG primer: basic principles of digital and analog EEG
New concepts in neonatal seizures
Neuroreport
Early diffusion-weighted MRI and 1H-magnetic resonance spectroscopy in asphyxiated full-term neonates
Biol Neonate
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Authors contributed equally to the work contained in this manuscript.