Erythropoietin signaling promotes oligodendrocyte development following prenatal systemic hypoxic-ischemic brain injury.

Erythropoietin signaling promotes oligodendrocyte development following prenatal systemic hypoxic-ischemic brain injury.
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DOI:
10.1038/pr.2013.155
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发表时间:
2013-12
期刊:
影响因子:
3.6
通讯作者:
Robinson, Shenandoah
Robinson, Shenandoah
中科院分区:
医学3区
文献类型:
--
作者:
Jantzie, Lauren L.;Miller, Robert H.;Robinson, Shenandoah

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早产引起的脑损伤会导致白色物质损伤(WMI),并导致慢性神经功能障碍,包括脑瘫、癫痫、认知和行为迟缓。未成熟的O4+少突胶质细胞特别容易受到损伤。了解发育中的大脑如何在受伤后恢复对于寻找更有效的治疗策略至关重要。促红细胞生成素(EPO)促进损伤后神经元的恢复,但其在促进少突胶质细胞谱系恢复中的作用尚不清楚。以前,我们发现重组EPO(rEPO)治疗增强MBP表达和功能恢复后,产前短暂性全身缺氧缺血(TSHI)的成年大鼠。我们假设,损伤后,rEPO将促进少突胶质细胞系细胞的发生,存活,成熟和髓鞘形成。体外试验用于确定rEPO如何促进TSHI后少突胶质细胞发育和恢复的特定阶段。在产前TSHI损伤后,rEPO促进少突胶质细胞前体细胞从少突胶质球的发生、少突胶质细胞前体细胞(OPCs)和O4+未成熟少突胶质细胞的存活、O4+细胞突起延伸和MBP表达。rEPO不改变OPC增殖。总之,这些研究表明,EPO信号促进产前TSHI损伤后少突胶质细胞谱系发育和恢复的关键阶段。促红细胞生成素治疗可能有利于早产儿和其他婴儿患者人群的发育性脑损伤的特点是脑损伤。
Brain injury from preterm birth causes white matter injury (WMI), and leads to chronic neurological deficits including cerebral palsy, epilepsy, cognitive and behavioral delay. Immature O4+ oligodendrocytes are particularly vulnerable to WMI. Understanding how the developing brain recovers after injury is essential to finding more effective therapeutic strategies. Erythropoietin (EPO) promotes neuronal recovery after injury however its role in enhancing oligodendroglial lineage recovery is unclear. Previously we found recombinant EPO (rEPO)-treatment enhances MBP expression and functional recovery in adult rats after prenatal transient systemic hypoxia-ischemia (TSHI). We hypothesized that after injury rEPO would enhance oligodendroglial lineage cell genesis, survival, maturation and myelination. In vitro assays were used to define how rEPO contributes to specific stages of oligodendrocyte development and recovery after TSHI. After prenatal TSHI injury, rEPO promotes genesis of oligodendrocyte progenitors from oligodendrospheres, survival of oligodendrocyte precursor cells (OPCs) and O4+ immature oligodendrocytes, O4+ cell process extension and MBP expression. rEPO did not alter OPC proliferation. Together, these studies demonstrate that EPO signaling promotes critical stages of oligodendroglial lineage development and recovery after prenatal TSHI injury. Erythropoietin treatment may be beneficial to preterm and other infant patient populations with developmental brain injury hallmarked by WMI.
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