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PS-339 Therapeutic Hypothermia In The Asphyctic Newborn: Immunohistochemical Comparison Of Three Cooling Target Temperatures In The Piglet Brain
  1. D Alonso Alconada1,
  2. K Broad1,
  3. A Bainbridge2,
  4. M Chandrasekaran1,
  5. SD Faulkner1,
  6. A Kerenyi1,
  7. KJ Hassell1,
  8. B Fleiss3,
  9. K Bennett1,
  10. D Kelen1,
  11. E Cady2,
  12. P Gressens3,
  13. X Golay4,
  14. NJ Robertson1
  1. 1Neonatology, Institute for Women’s Health University College London, London, UK
  2. 2Medical Physics and Bioengineering, University College London Hospitals NHS Trust, London, UK
  3. 3Perinatal Imaging and Health, Centre for the Developing Brain King’s College London, London, UK
  4. 4Brain Repair and Rehabilitation, Institute of Neurology University College London, London, UK


Background and aims Therapeutic hypothermia has now become standard of care for neonatal hypoxic-ischaemic brain injury, as it reduces death and neurological sequelae without neurodevelopmental disabilities. There are however around 40% of infants who, despite treatment, have an adverse neurodevelopmental outcome. We aimed to assess brain regional cell death and microglial activation with cooling to 35°C, 33.5°C, and 30°C after hypoxia-ischemia (HI) in the piglet asphyxia model.

Methods Following HI and resuscitation, 28 newborn piglets were randomised to: (i) normothermia (38.5°C throughout), or whole-body cooling 2–26 h post-insult to (ii) 35°C, (iii) 33.5°C, or (iv) 30°C (all groups n = 7). At 48 h after HI, regional neuropathological analysis was performed to assess delayed cell death (quantitative analyses of both TUNEL-positive cells and cleaved caspase 3 immunoreactivity) and microglial activation (Iba-1 staining).

Results Compared with normothermia, cooling to 33.5°C showed a strong reduction in delayed cell death in periventricular white matter, hippocampus, caudate, putamen, thalamus and midtemporal cortex, a beneficial effect also extended to other cortical areas when analysing microglial activation. Cooling to 35°C was also beneficial, but in fewer regions than at 33.5°C. On the contrary, cooling to 30°C neither reduced delayed cell death nor maintained the microglial ramification index, showing a global neuropathological pattern similar to that observed in the normothermic group.

Conclusions In our piglet perinatal asphyxia model, the optimum therapeutic hypothermia temperature is 33.5°C, thus suggesting that the extent of neuroprotection might not proportionately increase with temperature decreases.

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