Hypothermia is not therapeutic in a neonatal piglet model of inflammation-sensitized hypoxia-ischemia.
Hypothermia is not therapeutic in a neonatal piglet model of inflammation-sensitized hypoxia-ischemia.
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DOI：
10.1038/s41390-021-01584-6
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发表时间：
2022-05
影响因子：
3.6
通讯作者：
Robertson NJ
中科院分区：
文献类型：
--
作者：
Martinello KA;Meehan C;Avdic-Belltheus A;Lingam I;Mutshiya T;Yang Q;Akin MA;Price D;Sokolska M;Bainbridge A;Hristova M;Tachtsidis I;Tann CJ;Peebles D;Hagberg H;Wolfs TGAM;Klein N;Kramer BW;Fleiss B;Gressens P;Golay X;Robertson NJ
围产期炎症与缺氧缺血（HI）相结合，加重了发育中大脑的损伤。治疗性低温（HT）是新生儿脑病的标准护理;然而，其对炎症致敏HI（IS-HI）的益处尚不清楚。12头新生仔猪在52 h内接受2 µg/kg推注和1 µg/kg/h输注大肠杆菌脂多糖（LPS）。在LPS推注后4 h诱导HI。HI后，将仔猪随机分为HT组（HI后1-25小时，33.5 ℃，n = 6）或常温组（NT，n = 6）。在24和48 h记录振幅整合脑电图（aEEG）并采集磁共振波谱（MRS）。在48 h时，定量末端脱氧核苷酸转移酶dUTP缺口末端标记（TUNEL）阳性脑细胞死亡、小胶质细胞活化/增殖、星形胶质细胞增生和裂解的caspase-3（CC 3）。连续测量血液学和血浆细胞因子。两只HT仔猪死亡。各组间aEEG恢复、丘脑和白色物质MRS乳酸盐/N-乙酰天冬氨酸盐和TUNEL阳性细胞死亡相似。HT增加了尾状核中的小胶质细胞活化，但对胶质细胞活化/增殖没有其他影响。HT总体上降低了CC 3。HT抑制血小板计数和减弱白细胞增多。HT未改变细胞因子谱。我们没有观察到保护与HT在这个仔猪IS-HI模型的基础上aEEG，MRS，和免疫组化。HT的免疫抑制作用和LPS对抗神经炎症可能导致观察到的HT疗效缺乏。其他免疫调节策略可能在IS-HI中更有效。已知急性感染/炎症可加重围产期脑损伤，并可加重新生儿脑病的结局。治疗性HT是目前所有NE婴儿的护理标准，但合并感染/炎症婴儿的获益尚不清楚。在炎症（LPS）致敏HI的仔猪模型中，我们观察到没有证据表明冷却24小时的神经保护作用，基于我们的主要结局指标：aEEG，MRS Lac/NAA和组织学脑细胞死亡。具有有益免疫调节作用的其他神经保护剂需要在IS-HI模型中探索。
Perinatal inflammation combined with hypoxia–ischemia (HI) exacerbates injury in the developing brain. Therapeutic hypothermia (HT) is standard care for neonatal encephalopathy; however, its benefit in inflammation-sensitized HI (IS-HI) is unknown. Twelve newborn piglets received a 2 µg/kg bolus and 1 µg/kg/h infusion over 52 h of Escherichia coli lipopolysaccharide (LPS). HI was induced 4 h after LPS bolus. After HI, piglets were randomized to HT (33.5 °C 1–25 h after HI, n = 6) or normothermia (NT, n = 6). Amplitude-integrated electroencephalogram (aEEG) was recorded and magnetic resonance spectroscopy (MRS) was acquired at 24 and 48 h. At 48 h, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive brain cell death, microglial activation/proliferation, astrogliosis, and cleaved caspase-3 (CC3) were quantified. Hematology and plasma cytokines were serially measured. Two HT piglets died. aEEG recovery, thalamic and white matter MRS lactate/N-acetylaspartate, and TUNEL-positive cell death were similar between groups. HT increased microglial activation in the caudate, but had no other effect on glial activation/proliferation. HT reduced CC3 overall. HT suppressed platelet count and attenuated leukocytosis. Cytokine profile was unchanged by HT. We did not observe protection with HT in this piglet IS-HI model based on aEEG, MRS, and immunohistochemistry. Immunosuppressive effects of HT and countering neuroinflammation by LPS may contribute to the observed lack of HT efficacy. Other immunomodulatory strategies may be more effective in IS-HI. Acute infection/inflammation is known to exacerbate perinatal brain injury and can worsen the outcomes in neonatal encephalopathy. Therapeutic HT is the current standard of care for all infants with NE, but the benefit in infants with coinfection/inflammation is unknown. In a piglet model of inflammation (LPS)-sensitized HI, we observed no evidence of neuroprotection with cooling for 24 h, based on our primary outcome measures: aEEG, MRS Lac/NAA, and histological brain cell death. Additional neuroprotective agents, with beneficial immunomodulatory effects, require exploration in IS-HI models.
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DOI：
10.1016/j.jpeds.2018.07.041
发表时间：
2018-12
期刊：
The Journal of pediatrics
影响因子：
--
作者：
Basu SK;Ottolini K;Govindan V;Mashat S;Vezina G;Wang Y;Ridore M;Chang T;Kaiser JR;Massaro AN
通讯作者：
Massaro AN
影响因子：
9.3
作者：
Fleiss B;Nilsson MK;Blomgren K;Mallard C
通讯作者：
Mallard C
影响因子：
3.4
作者：
Eklind, S;Mallard, C;Hagberg, H
通讯作者：
Hagberg, H
影响因子：
8.3
作者：
Alonso-Alconada D;Broad KD;Bainbridge A;Chandrasekaran M;Faulkner SD;Kerenyi Á;Hassell J;Rocha-Ferreira E;Hristova M;Fleiss B;Bennett K;Kelen D;Cady E;Gressens P;Golay X;Robertson NJ
通讯作者：
Robertson NJ
影响因子：
5.6
作者：
Charriaut-Marlangue C;Besson VC;Baud O
通讯作者：
Baud O