Neurologic effects of short-term treatment with a soluble epoxide hydrolase inhibitor after cardiac arrest in pediatric swine.
Neurologic effects of short-term treatment with a soluble epoxide hydrolase inhibitor after cardiac arrest in pediatric swine.
复制标题
DOI：
10.1186/s12868-020-00596-y
复制
发表时间：
2020-10-31
期刊：
影响因子：
2.4
通讯作者：
Martin LJ
中科院分区：
文献类型：
--
作者：
O'Brien CE;Santos PT;Kulikowicz E;Lee JK;Koehler RC;Martin LJ
心脏骤停（CA）是儿童急性神经损伤的最常见原因。许多幸存者在恢复1年时有明显的神经认知缺陷。环氧二十碳三烯酸（Epoxyeicosatrienoic acids，ESTs）是一种多功能的内源性脂质信号分子，参与脑病理学，可能具有治疗相关性。然而，雌二醇通过可溶性环氧化物水解酶（sEH）快速代谢为活性较低的二羟基二十碳三烯酸，限制了它们的生物利用度。我们假设sEH抑制将改善幼年猪模型中CA后的结果。雄性仔猪（3-4 kg，2周龄）进行缺氧窒息CA。复苏后，他们被随机分配到静脉治疗sEH抑制剂（TPPU，1 mg/kg; n = 8）或车辆（10%聚（乙二醇）; n = 9）在30分钟和24小时后恢复自主循环。两个假手术组接受TPPU（n = 9）或溶剂（n = 8）。在4天存活者的壳核和运动皮质的苏木精和伊红染色切片中计数神经元。CA +媒介物组中的仔猪在壳核和运动皮质中的神经元比假手术动物少。然而，CA后的神经元数量在两个解剖区域的溶剂组和TPPU处理组之间没有差异。此外，Sham + TPPU组中20%的壳核神经元具有异常形态，具有细胞体磨损和核浓缩。TPPU治疗也没有减少神经功能缺损。在窒息CA复苏后30分钟和24小时使用sEH抑制剂治疗不能保护仔猪的神经元或改善其急性神经学结局。
Cardiac arrest (CA) is the most common cause of acute neurologic insult in children. Many survivors have significant neurocognitive deficits at 1 year of recovery. Epoxyeicosatrienoic acids (EETs) are multifunctional endogenous lipid signaling molecules that are involved in brain pathobiology and may be therapeutically relevant. However, EETs are rapidly metabolized to less active dihydroxyeicosatrienoic acids by soluble epoxide hydrolase (sEH), limiting their bioavailability. We hypothesized that sEH inhibition would improve outcomes after CA in an infant swine model. Male piglets (3–4 kg, 2 weeks old) underwent hypoxic-asphyxic CA. After resuscitation, they were randomized to intravenous treatment with an sEH inhibitor (TPPU, 1 mg/kg; n = 8) or vehicle (10% poly(ethylene glycol); n = 9) administered at 30 min and 24 h after return of spontaneous circulation. Two sham-operated groups received either TPPU (n = 9) or vehicle (n = 8). Neurons were counted in hematoxylin- and eosin-stained sections from putamen and motor cortex in 4-day survivors. Piglets in the CA + vehicle groups had fewer neurons than sham animals in both putamen and motor cortex. However, the number of neurons after CA did not differ between vehicle- and TPPU-treated groups in either anatomic area. Further, 20% of putamen neurons in the Sham + TPPU group had abnormal morphology, with cell body attrition and nuclear condensation. TPPU treatment also did not reduce neurologic deficits. Treatment with an sEH inhibitor at 30 min and 24 h after resuscitation from asphyxic CA does not protect neurons or improve acute neurologic outcomes in piglets.
登录
查看更多内容
影响因子：
2.9
作者：
Ostermann AI;Herbers J;Willenberg I;Chen R;Hwang SH;Greite R;Morisseau C;Gueler F;Hammock BD;Schebb NH
通讯作者：
Schebb NH
影响因子：
5.7
作者：
Lee JK;Yang ZJ;Wang B;Larson AC;Jamrogowicz JL;Kulikowicz E;Kibler KK;Mytar JO;Carter EL;Burman HT;Brady KM;Smielewski P;Czosnyka M;Koehler RC;Shaffner DH
通讯作者：
Shaffner DH
影响因子：
2.9
作者：
Inceoglu B;Bettaieb A;Haj FG;Gomes AV;Hammock BD
通讯作者：
Hammock BD
影响因子：
4.2
作者：
Lok, J;Martin, LJ
通讯作者：
Martin, LJ
影响因子：
11.2
作者：
Martin, LJ;Brambrink, AM;Traystman, RJ
通讯作者：
Traystman, RJ