ELECTROPHYSIOLOGICAL ASSESSMENT OF HYPOXIC-ISCHEMIC ENCEPHALOPATHY (HIE) IN NEWBORN PIGS
Objectives: The newborn pig is a translational model of neonatal HIE. Neuroprotective HIE management is currently limited to therapeutic hypothermia (THT, Tcore=33.5°C). Therefore, our major aim was to investigate if THT combined with other treatments such as H2 or graded restoration of normocapnia (GRN) after asphyxia (ASPH) could afford better outcome evaluated with EEG and visual evoked potential (VEP). Methods: Anesthetized, ventilated, male newborn pigs (<24h, 1.5-2 kg, n=34) were divided into 5 experimental groups: time control, ASPH+normothermia, ASPH+THT, ASPH+THT+H2, and ASPH+THT+GRN. ASPH (20 min) was evoked with 20%CO2 and 4%O2 gas mixture ventilation. Reoxygenation was commenced with 21%O2, or 21%O2+2.1%H2 (4h), or 21%O2+10-then-5%CO2 (2-2h). EEG was recorded throughout the 48h survival period, while VEPs (1 Hz) were evoked at 24h and 48h. The power spectral density (PSD) analyses were performed with MATLAB, EEGLAB©. Results: Compared to time controls, PSD-s and VEP amplitudes were significantly reduced in normothermic ASP animals. Moreover, abnormal waveforms/spikes, generalized seizures were also recorded in this group. These events were largely missing in the THT groups, and although the PSDs and VEPs were not recovered, yet the former indicated better outcome. However, H2 and/or GRN did not appear to provide additional benefits to THT alone. Conclusions: PSDs and VEP reflect the severe HIE development in our model, and the neuroprotective effect of THT can be detected. Our methods seem sufficient to test further putative neuroprotective HIE therapies. Support: Hungarian Brain Research Program 2.0 (2017-2.1 NKP 2017 00002), the EU-funded Hungarian grant EFOP-3.6.1-16-2016-00008 and the GINOP 2.3.2 15 2016 00034. V.K. is supported by OTKA-PD128464 from the NRDI.