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Neither xenon nor fentanyl induce neuroapoptosis in the newborn pig brain, however isoflurane does

Presented at the Neonatal Society 2012 Autumn Meeting.

Sabir H1, Bishop S1, Cohen N3, Maes E2, Liu X1, Dingley J4, Thoresen M1,2

1 School of Clinical Sciences, University of Bristol, St Michael’s Hospital, Bristol, UK
2 Department of Physiology, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
3 Neuropathology, School of Clinical Sciences, University of Bristol, Frenchay Hospital, Bristol, UK
4 Swansea Medical School, Singleton Park, Swansea,UK

Background: Common general anesthetic agents may harm the developing brain. Some N-methyl- D-aspartate (NMDA) antagonists may induce neuronal injury and cell death during brain development. Xenon doubles neuroprotection when combined with therapeutic hypothermia after hypoxic-ischemic brain injury in newborn animals. This study examines the neuroapoptotic effect of breathing 50% xenon with high-dose fentanyl for 24h at normothermia (NT) or hypothermia (HT) or breathing 2% isoflurane only at NT on healthy newborn pigs.

Methods: There were 31 pigs (<24h old) and 5 treatment groups: (1) 24h of 50% inhaled xenon (Xe50%) with fentanyl sedation at HT (Trec=33.5°C), (2) 24h of Xe50% with fentanyl sedation at NT (Trec=38.5°C), (3) 24h of fentanyl sedation at NT, (4) non ventilated juvenile controls at NT or (5) 24h of inhaled 2% isoflurane at NT. Animals were sacrificed after 24h of allocated treatment and brains prepared for histology. Pathological cells were assessed in different brain regions and apoptotic cells were counted after immunostaining (caspase-3 and TUNEL).

Results: Neuropathological assessment did not show a significant difference in apoptosis for examined brain regions between treatment groups (1) – (4), but a large increase in apoptosis when isoflurane was used. The numbers of apoptotic cells, assessed by cleaved caspase-3 and TUNEL-staining, were significantly increased in the isoflurane group for cortex, hippocampus and white matter. For groups (1) – (4) regression analysis indicated that hypothermia gave a small, but statistically significant increase in the number of immunostained cells in cerebral cortex and white matter (p<0.05).

Conclusion: At NT or HT, neither 24h of inhaled 50% xenon with fentanyl sedation, nor fentanyl alone, induce neuroapoptosis in the neonatal pig brain. Breathing 2% isoflurane does increase neuroapoptosis in neonatal pigs.

Corresponding author: marianne.thoresen@bristol.ac.uk

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