Recombinant erythropoietin does not augment hypothermic white matter protection after global cerebral ischaemia in near-term fetal sheep.
Recombinant erythropoietin does not augment hypothermic white matter protection after global cerebral ischaemia in near-term fetal sheep.
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DOI：
10.1093/braincomms/fcab172
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发表时间：
2021
影响因子：
4.8
通讯作者：
Gunn AJ
中科院分区：
文献类型：
--
作者：
Wassink G;Davidson JO;Crisostomo A;Zhou KQ;Galinsky R;Dhillon SK;Lear CA;Bennet L;Gunn AJ
缺氧缺血性脑病的低温治疗可提供部分白色物质保护。重组促红细胞生成素可减少缺氧缺血后的脱髓鞘，但促红细胞生成素辅助治疗能否进一步改善治疗性低温后的预后尚不清楚。足月胎羊接受假缺血（n = 9）或脑缺血30分钟（缺血-溶媒，n = 8），随后静脉输注重组促红细胞生成素缺血-Epo组8例; 5000 IU/kg推注剂量，然后833.3 IU/kg/h），脑低温（缺血-低体温，n = 8），或重组促红细胞生成素加低体温（缺血-Epo-低体温，n = 8），从缺血后3至72小时。在脑缺血后7天收获胎脑。缺血与总Olig 2阳性少突胶质细胞的显着损失、髓鞘密度降低和白色物质束线性度降低（P < 0.01）、小胶质细胞诱导和caspase-3阳性细胞凋亡增加有关。脑低温可使少突胶质细胞总数增加，髓鞘碱性蛋白恢复（P < 0.01），而重组促红细胞生成素可部分改善髓鞘碱性蛋白密度和纤维束线性。两种干预均抑制小胶质细胞增生和caspase-3（P < 0.05）。与低温相比，联合治疗改善了2′，3 ′-环核苷酸3′-磷酸二酯酶-髓鞘密度，但没有其他累加效应。这些研究结果表明，虽然低温和重组促红细胞生成素独立保护严重缺氧缺血后的白色物质，它们具有部分重叠的抗炎和抗凋亡作用，联合治疗的附加效益很小。Wassink等人报告称，在近期胎羊中，诱导低温和高剂量重组促红细胞生成素输注在脑缺血后3小时开始，持续3天，7天恢复后独立保护了白色物质。然而，有重叠的抗炎和抗凋亡作用，与联合治疗的附加效益很少。
Therapeutic hypothermia for hypoxic-ischaemic encephalopathy provides partial white matter protection. Recombinant erythropoietin reduces demyelination after hypoxia-ischaemia, but it is unclear whether adjunct erythropoietin treatment can further improve outcomes after therapeutic hypothermia. Term-equivalent fetal sheep received sham-ischaemia (n = 9) or cerebral ischaemia for 30 min (ischaemia-vehicle, n = 8), followed by intravenous infusion of recombinant erythropoietin (ischaemia-Epo, n = 8; 5000 IU/kg bolus dose, then 833.3 IU/kg/h), cerebral hypothermia (ischaemia-hypothermia, n = 8), or recombinant erythropoietin plus hypothermia (ischaemia-Epo-hypothermia, n = 8), from 3 to 72 h post-ischaemia. Foetal brains were harvested at 7 days after cerebral ischaemia. Ischaemia was associated with marked loss of total Olig2-positive oligodendrocytes with reduced density of myelin and linearity of the white matter tracts (P < 0.01), and microglial induction and increased caspase-3-positive apoptosis. Cerebral hypothermia improved the total number of oligodendrocytes and restored myelin basic protein (P < 0.01), whereas recombinant erythropoietin partially improved myelin basic protein density and tract linearity. Both interventions suppressed microgliosis and caspase-3 (P < 0.05). Co-treatment improved 2′,3′-cyclic-nucleotide 3′-phosphodiesterase-myelin density compared to hypothermia, but had no other additive effect. These findings suggest that although hypothermia and recombinant erythropoietin independently protect white matter after severe hypoxia-ischaemia, they have partially overlapping anti-inflammatory and anti-apoptotic effects, with little additive benefit of combination therapy. Wassink et al. report that in near-term fetal sheep induced hypothermia and high-dose recombinant erythropoietin infusion started 3 h after cerebral ischaemia and continued for 3 days, independently protected white matter after 7 days recovery. However, there were overlapping anti-inflammatory and anti-apoptotic effects, with little additive benefit of combination therapy.
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影响因子：
3.3
作者：
Mallard C;Tremblay ME;Vexler ZS
通讯作者：
Vexler ZS
影响因子：
5.6
作者：
Dhillon, Simerdeep K.;Wassink, Guido;Bennet, Laura
通讯作者：
Bennet, Laura
影响因子：
8
作者：
Gunn, AJ;Gunn, TR;Gluckman, PD
通讯作者：
Gluckman, PD
影响因子：
2.5
作者：
Heursen, Eva-Marie;Zuazo Ojeda, Amaya;Lubian Lopez, Simon Pedro
通讯作者：
Lubian Lopez, Simon Pedro
DOI：
10.1136/archdischild-2018-316509
发表时间：
2020-01-01
影响因子：
4.4
作者：
Lee-Kelland, Richard;Jary, Sally;Chakkarapani, Ela
通讯作者：
Chakkarapani, Ela