Intranasal epidermal growth factor treatment rescues neonatal brain injury. (Nature, 2013)

報告日期: 2014/05/23
報告時間: 4:00/4:50
報告學生: 黃家葳
講評老師: 許鍾瑜
附件下載: 下載[1412-1396957760-1.pdf] 

Intranasal epidermal growth factor treatment rescues neonatal brain injury

Joseph Scafidi1,2, Timothy R. Hammond1,3, Susanna Scafidi4, Jonathan Ritter1, Beata Jablonska1, Maria Roncal1, KlaraSzigeti-Buck5, Daniel Coman6, Yuegao Huang6, Robert J. McCarter Jr7, Fahmeed Hyder6, Tamas L. Horvath5 & Vittorio Gallo1

Nature 506, 230–234 (2014)

Speaker: Chia-Wei Huang                     Date: 2014/05/23 16:00-16:50

Commentator: Jung-Yu Hsu                   Location: Room 602



White matter injury in neonatal brain results from chronic hypoxia may impair neurodevelopment and cause a lifelong sensorimotor deficit. Diffuse white matter injury (DWMI), one of common neonatal brain injure without effective therapy, is failure in oligodengrocyte maturation. In previous study, enhanced epidermal growth factor receptor (EGFR) signaling was considered to promote oligodendrogenesis. Therefore, this paper aims to investigate the role of EGFR signaling in EGFR-expressing cells to promote its endogenous response. And, to study the effect of EGFR on structural and functional recovery in a critical period after DWMI. The neonatal DWMI was created by placing the mice into hypoxia chamber which contained only 10.5% oxygen on postnatal day 3-11. The mice expressing enhanced green fluorescent protein under CNP promoter (Rep mice) and Rep mice overexpressing human EGFR under the same promoter were used in this model. The complex running wheel task and the inclined beam-walking task were performed to examine subcortical white-matter-dependent sensorimotor function. Overexpression of EGFR in oligodendrocyte lineage cells in transgenic mice or intranasally administered of heparin-binding EGF showed to decreases oligodendrocyte death, and increased the generation of new oligodendrocytes. Recovery in myelin structure integrity was observed by electron microscopy and diffusion tensor imaging. Furthermore, overexpression of EGFR and activation of EGFR signaling prevented the deficit in white-matter-dependent sensorimotor function. Blockage of EGFR signaling by its antagonist decreased oligodendrocyte number and the regeneration of oligodendrocytes, which indicated the role of endogenous EGFR signaling in recovery of white matter injury. Taken together, the results suggested that active EGFR signaling can promote cellular and functional recovery after neonatal DWMI.



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