PDF(Pubmed)
Abstract：
Hypoxic-ischemic encephalopathy (HIE), resulting from a lack of blood flow and oxygen before or during newborn delivery, is a leading cause of cerebral palsy and neurological disability in children. Therapeutic hypothermia (TH), the current standard of care in HIE, is only beneficial in 1 of 7-8 cases. Therefore, there is a critical need for more efficient treatments. We have previously reported that omega-3 (n-3) fatty acids (FA) carried by triglyceride (TG) lipid emulsions provide neuroprotection after experimental hypoxic-ischemic (HI) injury in neonatal mice. Herein, we propose a novel acute therapeutic approach using an n-3 diglyceride (DG) lipid emulsions. Importantly, n-3 DG preparations had much smaller particle size compared to commercially available or lab-made n-3 TG emulsions. We showed that n-3 DG molecules have the advantage of incorporating at substantially higher levels than n-3 TG into an in vitro model of phospholipid membranes. We also observed that n-3 DG after parenteral administration in neonatal mice reaches the bloodstream more rapidly than n-3 TG. Using neonatal HI brain injury models in mice and rats, we found that n-3 DG emulsions provide superior neuroprotection than n-3 TG emulsions or TH in decreasing brain infarct size. Additionally, we found that n-3 DGs attenuate microgliosis and astrogliosis. Thus, n-3 DG emulsions are a superior, promising, and novel therapy for treating HIE.
摘要：
缺氧缺血性脑病(HIE),由于新生儿分娩前或分娩过程中缺乏血液和氧气，是儿童脑瘫和神经系统残疾的主要原因。治疗性低温（TH），HIE目前的护理标准，仅在7-8个病例中的1个中有益。因此,迫切需要更有效的治疗方法。我们以前曾报道过，甘油三酸酯（TG）脂质乳剂携带的omega-3（n-3）脂肪酸（FA）在新生小鼠的实验性缺氧缺血性（HI）损伤后提供神经保护。在这里，我们提出了一种使用n-3甘油二酯（DG）脂质乳剂的新型急性治疗方法。重要的是,与市售可得的或实验室制备的n-3TG乳液相比,n-3DG制剂具有小得多的粒度。我们表明，n-3DG分子具有以明显高于n-3TG的水平掺入磷脂膜体外模型的优势。我们还观察到，新生小鼠肠胃外给药后，n-3DG比n-3TG更快地到达血流。使用小鼠和大鼠的新生儿HI脑损伤模型，我们发现n-3DG乳剂在减少脑梗塞面积方面比n-3TG乳剂或TH乳剂具有更好的神经保护作用.此外,我们发现n-3DG可减轻小胶质细胞增生和星形胶质细胞增生。因此，n-3DG乳液是一种优越的，有希望的,和治疗HIE的新疗法。
