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

Acute Injection of Omega-3 Triglyceride Emulsion Provides Very Similar Protection as Hypothermia in a Neonatal Mouse Model of Hypoxic-Ischemic Brain Injury.
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DOI:
10.3389/fneur.2020.618419
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发表时间:
2020
影响因子:
3.4
通讯作者:
Deckelbaum RJ
Deckelbaum RJ
中科院分区:
医学3区
文献类型:
--
作者:
Manual Kollareth DJ;Zirpoli H;Ten VS;Deckelbaum RJ

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治疗性低温(HT)是目前公认的新生儿窒息的治疗方法,也是治疗成人卒中的一种有前途的策略。我们以前报道过,急性给药二十二碳六烯酸(DHA)甘油三酯乳剂(tri-DHA)保护新生小鼠免受缺氧缺血(HI)损伤。我们质疑HT和tri-DHA联合治疗是否会在保护大脑免受HI损伤方面产生协同作用。将经受HI损伤的新生小鼠(10日龄)置于温度控制室中4小时的HT(直肠温度31-32°C)或常温(NT,直肠温度37°C)。在HT开始之前和之后1小时,用tri-DHA(0.375 g tri-DHA/kg bw,两次注射)处理小鼠。我们观察到,在HI损伤后立即开始的HT减少了脑梗死体积,与tri-DHA治疗相似(约50%)。此外,HI损伤后延迟2小时的HT提供神经保护(%梗塞体积:31.4 ± 4.1对18.8 ± 4.6 HT),而延迟4小时的HT不能保护免受HI损伤(%梗塞体积:30.7 ± 5.0对31.3 ± 5.6 HT)。与单独HT相比,在HI损伤后0或2小时开始的HT加tri-DHA组合治疗没有进一步减少梗死体积。我们的研究结果表明,HT提供了类似程度的神经保护HI损伤相比,三DHA治疗。HT只能在三级护理中心提供,需要密切监测,并可能产生不良影响。相比之下,三-DHA治疗可能有利于为HI损伤后的患者提供可行且有效的策略。
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.
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