PS-339 Therapeutic Hypothermia In The Asphyctic Newborn: Immunohistochemical Comparison Of Three Cooling Target Temperatures In The Piglet Brain

Autor: Aron Kerenyi, Kate Bennett, D Kelen, Alan Bainbridge, Xavier Golay, M Chandrasekaran, Stuart Faulkner, D Alonso Alconada, Nicola J. Robertson, Bobbi Fleiss, Pierre Gressens, EB Cady, KJ Hassell, Kevin D. Broad
Rok vydání: 2014
Předmět:
Zdroj: Archives of Disease in Childhood. 99:A234.2-A234
ISSN: 1468-2044
0003-9888
Popis: 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.
Databáze: OpenAIRE
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