Acute Injection of Omega-3 Triglyceride Emulsion Provides Very Similar Protection as Hypothermia in a Neonatal Mouse Model of Hypoxic-Ischemic Brain Injury

Abstract

Therapeutic hypothermia (HT) is a currently accepted treatment for neonatal asphyxia and is a promising strategy in adult stroke therapy. We previously reported that acute administration of docosahexaenoic acid (DHA) triglyceride emulsion (tri-DHA) protects against hypoxic-ischemic (HI) injury in neonatal mice. We questioned if co-treatment with HT and tri-DHA would achieve synergic effects in protecting the brain from HI injury. Neonatal mice (10-day old) subjected to HI injury were placed in temperature-controlled chambers for 4 h of either HT (rectal temperature 31–32°C) or normothermia (NT, rectal temperature 37°C). Mice were treated with tri-DHA (0.375 g tri-DHA/kg bw, two injections) before and 1 h after initiation of HT. We observed that HT, beginning immediately after HI injury, reduced brain infarct volume similarly to tri-DHA treatment (~50%). Further, HT delayed 2 h post-HI injury provided neuroprotection (% infarct volume: 31.4 ± 4.1 vs. 18.8 ± 4.6 HT), while 4 h delayed HT did not protect against HI insult (% infarct volume: 30.7 ± 5.0 vs. 31.3 ± 5.6 HT). HT plus tri-DHA combination treatment beginning at 0 or 2 h after HI injury did not further reduce infarct volumes compared to HT alone. Our results indicate that HT offers similar degrees of neuroprotection against HI injury compared to tri-DHA treatment. HT can only be provided in tertiary care centers, requires intense monitoring and can have adverse effects. In contrast, tri-DHA treatment may be advantageous in providing a feasible and effective strategy in patients after HI injury.

Long-chain omega-3 polyunsaturated fatty acids are reduced in neonates with substantial brain injury undergoing therapeutic hypothermia after hypoxic–ischemic encephalopathy

“…A study in newborn piglets (within 36 h after birth) showed that combining DHA with therapeutic hypothermia does not appear to provide additional benefits to either therapeutic hypothermia or DHA alone, when the hypoxic ischemic injury outcomes were assessed at 9.5 h after injury ( 12 ). In a more recent study in neonatal mice (10-day old) subjected to hypoxic ischemic injury, DHA and therapeutic hypothermia did not synergize, as assessed in terms of infarct size at 24 h post-injury ( 12 , 46 ). Therefore, these reports in different species and with assessment of different outcomes at varied times post-injury, do not allow to reach a definitive conclusion as to the additional potential benefit of using DHA in therapeutic hypothermia-exposed neonates.…”