Author/Editor		Wood, Thomas; Gundersen, Julia K.; Falck, Mari; Maes, Elke; Osredkar, Damjan; Loberg, Else Marit; Sabir, Hemmen; Walloe, Lars; Thoresen, Marianne
Title		Variability and sex-dependence of hypothermic neuroprotection in a rat model of neonatal hypoxic-ischaemic brain injury
Type		članek
Vol. and No.		Letnik 10, št. 1
Publication year		2020
Volume		str. [1-13]
ISSN		2045-2322 - Scientific reports
Language		eng
Abstract		Therapeutic hypothermia (HT) is standard care for term infants with hypoxic-ischaemic (HI) encephalopathy. However, the efficacy of HT in preclinical models, such as the Vannucci model of unilateral HI in the newborn rat, is often greater than that reported from clinical trials. Here, we report a meta-analysis of data from every experiment in a single laboratory, including pilot data, examining the effect of HT in the Vannucci model. Across 21 experiments using 106 litters, median (95% CI) hemispheric area loss was 50.1% (46.0-51.9%; n = 305) in the normothermia group, and 41.3% (35.1-44.9%; n = 317) in the HT group, with a bimodal injury distribution. Median neuroprotection by HT was 17.6% (6.8-28.3%), including in severe injury, but was highly-variable across experiments. Neuroprotection was significant in females (p < 0.001), with a non-significant benefit in males (p = 0.07). Animals representing the median injury in each group within each litter (n = 277, 44.5%) were also analysed using formal neuropathology, which showed neuroprotection by HT throughout the brain, particularly in females. Our results suggest an inherent variability and sex-dependence of the neuroprotective response to HT, with the majority of studies in the Vannucci model vastly underpowered to detect true treatment effects due to the distribution of injury.
Keywords		neonatalna hipoksično-ishemična poškodba možganov terapevtska hipotermija Vannuccijev model neonatal hypoxic-ischaemic brain injury therapeutic hypothermia Vannucci model