Leukemia inhibitor factor promotes functional recovery and oligodendrocyte survival in rat models of focal ischemia.
Leukemia inhibitor factor promotes functional recovery and oligodendrocyte survival in rat models of focal ischemia.
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DOI：
10.1111/ejn.12675
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发表时间：
2014-10
期刊：
影响因子：
--
通讯作者：
Pennypacker KR
中科院分区：
文献类型：
--
作者：
Rowe DD;Collier LA;Seifert HA;Chapman CB;Leonardo CC;Willing AE;Pennypacker KR
人类脐带血(HUCB)细胞已经在局灶性脑缺血的啮齿动物模型和概括中风情况的体外系统中显示出有效性。一种潜在的保护机制是通过分泌保护神经元和少突胶质细胞(OLs)免受氧化应激的可溶性因子。为了克服细胞疗法的实际问题，识别HUCB和其他干细胞释放的可溶性因子可能会为更多比例的中风患者提供更安全的治疗方式铺平道路。在这些可溶性因子中有白血病抑制因子(LIF)，这是一种对细胞存活发挥多效性作用的细胞因子。在这里，数据表明，LIF有效地减少了脑梗塞体积，减少了白质损伤，并改善了永久性大脑中动脉闭塞后的大鼠的功能结果。为了进一步探索下游信号，原代培养的少突胶质细胞暴露在氧糖剥夺(OGD)中以模拟中风条件。LiF可显著减少OL乳酸脱氢酶释放，降低超氧化物歧化酶活性，并诱导过氧化还蛋白4(Prdx4)转录本。此外，Akt的抑制和与Prdx4中和抗体的共同孵育，都否定了LIF的保护和抗氧化能力，确立了Akt信号通路和Prdx4介导的抗氧化在LIF保护中的作用。
Human umbilical cord blood (HUCB) cells have shown efficacy in rodent models of focal ischemia and in vitro systems that recapitulate stroke conditions. One potential mechanism of protection is through secretion of soluble factors that protect neurons and oligodendrocytes (OLs) from oxidative stress. To overcome practical issues with cellular therapies, identification of soluble factors released by HUCB and other stem cells may pave the way for treatment modalities that are safer for a larger percentage of stroke patients. Among these soluble factors is leukemia inhibitory factor (LIF), a cytokine that exerts pleiotropic effects on cell survival. Here, data show that LIF effectively reduced infarct volume, reduced white matter injury and improved functional outcomes when administered to rats following permanent middle cerebral artery occlusion. To further explore downstream signaling, primary oligodendrocyte cultures were exposed to oxygen glucose deprivation (OGD) to mimic stroke conditions. LIF significantly reduced lactate dehydrogenase release from OLs, reduced superoxide dismutase activity, and induced peroxiredoxin 4 (Prdx4) transcript. Additionally, the protective and antioxidant capacity of LIF was negated by both Akt inhibition and co-incubation with Prdx4 neutralizing antibodies, establishing a role for the Akt signaling pathway and Prdx4-mediated antioxidation in LIF protection.
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DOI：
10.1083/jcb.85.3.890
发表时间：
1980-06
期刊：
The Journal of cell biology
影响因子：
--
作者：
McCarthy KD;de Vellis J
通讯作者：
de Vellis J
影响因子：
2.1
作者：
Ajmo, Craig T., Jr.;Vernon, Dionne O. L.;Cuevas, Javier
通讯作者：
Cuevas, Javier
影响因子：
2.9
作者：
Duckworth, EAM;Butler, TL;Pennypacker, KR
通讯作者：
Pennypacker, KR
影响因子：
3.3
作者：
Hendriks, Jerome J. A.;Slaets, Helena;Hellings, Niels
通讯作者：
Hellings, Niels
影响因子：
4.2
作者：
Hall, A. A.;Guyer, A. G.;Leonardo, C. C.;Ajmo, C. T., Jr.;Collier, L. A.;Willing, A. E.;Pennypacker, K. R.
通讯作者：
Pennypacker, K. R.