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Supplementary Material for: Intravenous Edaravone plus Therapeutic Hypothermia Offers Limited Neuroprotection in the Hypoxic-Ischaemic Newborn Piglet

posted on 28.10.2020, 10:06 by Yamato S.H., Nakamura S., Htun Y., Nakamura M., Jinnai W., Nakao Y., Mitsuie T., Koyano K., Wakabayashi T., Morimoto A.H., Sugino M., Iwase T., Kondo S.I., Yasuda S., Ueno M., Miki T., Kusaka T.
Background: Therapeutic hypothermia (TH) is a standard therapy for neonatal hypoxic-ischaemic encephalopathy. One potential additional therapy is the free radical scavenger edaravone (EV; 3-methyl-1-phenyl-2-pyrazolin-5-one). Objectives and Methods: This study aimed to compare the neuroprotective effects of edaravone plus therapeutic hypothermia (TH + EV) with those of TH alone after a hypoxic-ischaemic insult in the newborn piglet. Anaesthetized piglets were subjected to 40 min of hypoxia (3–5% inspired oxygen), and cerebral ischaemia was assessed using cerebral blood volume. Body temperature was maintained at 39.0 ± 0.5°C in the normothermia group (NT, n = 8) and at 33.5 ± 0.5°C (24 h after the insult) in the TH (n = 7) and TH + EV (3 mg/kg intravenous every 12 h for 3 days after the insult; n = 6) groups under mechanical ventilation. Results: Five days after the insult, the mean (standard deviation) neurological scores were 10.9 (5.7) in the NT group, 17.0 (0.4) in the TH group (p = 0.025 vs. NT), and 15.0 (3.9) in the TH + EV group. The histopathological score of the TH + EV group showed no significant improvement compared with that of the other groups. Conclusion: TH + EV had no additive neuroprotective effects after hypoxia-ischaemia in neurological and histopathological assessments.