Intravenous Edaravone plus Therapeutic Hypothermia Offers Limited Neuroprotection in the Hypoxic-Ischaemic Newborn Piglet

Neonatology. 2020;117(6):713-720. doi: 10.1159/000511085. Epub 2020 Oct 28.

Abstract

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.

Keywords: Edaravone; Hypoxic-ischemic encephalopathy; Piglet; Therapeutic hypothermia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Brain
  • Disease Models, Animal
  • Edaravone
  • Hypothermia, Induced*
  • Hypoxia
  • Hypoxia-Ischemia, Brain* / therapy
  • Ischemia
  • Neuroprotection
  • Swine

Substances

  • Edaravone