Epidermal growth factor preserves myelin and promotes astrogliosis after intraventricular hemorrhage

Govindaiah Vinukonda, Furong Hu, Rana Mehdizadeh, Preeti Dohare, Ali Kidwai, Ankit Juneja, Vineet Naran, Maria Kierstead, Rachit Chawla, Robert Kayton, Praveen Ballabh

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Intraventricular hemorrhage (IVH) leads to reduced myelination and astrogliosis of the white matter in premature infants. No therapeutic strategy exists to minimize white matter injury in survivors with IVH. Epidermal growth factor (EGF) enhances myelination, astrogliosis, and neurologic recovery in animal models of white matter injury. Here, we hypothesized that recombinant human (rh) EGF treatment would enhance oligodendrocyte precursor cell (OPC) maturation, myelination, and neurological recovery in preterm rabbits with IVH. In addition, rhEGF would promote astrogliosis by inducing astroglial progenitor proliferation and GFAP transcription. We tested these hypotheses in a preterm rabbit model of IVH and evaluated autopsy samples from human preterm infants. We found that EGF and EGFR expression were more abundant in the ganglionic eminence relative to the cortical plate and white matter of human infants and that the development of IVH reduced EGF levels, but not EGFR expression. Accordingly, rhEGF treatment promoted proliferation and maturation of OPCs, preserved myelin in the white matter, and enhanced neurological recovery in rabbits with IVH. rhEGF treatment inhibited Notch signaling, which conceivably contributed to OPC maturation. rhEGF treatment contributed to astrogliosis by increasing astroglial proliferation and upregulating GFAP as well as Sox9 expression. Hence, IVH results in a decline in EGF expression; and rhEGF treatment preserves myelin, restores neurological recovery, and exacerbates astrogliosis by inducing proliferation of astrocytes and enhancing transcription of GFAP and Sox9 in pups with IVH. rhEGF treatment might improve the neurological outcome of premature infants with IVH. GLIA 2016;64:1987–2004.

Original languageEnglish (US)
Pages (from-to)1987-2004
Number of pages18
JournalGlia
Volume64
Issue number11
DOIs
StatePublished - Nov 1 2016
Externally publishedYes

Keywords

  • astrogliosis
  • epidermal growth factor
  • intraventricular hemorrhage
  • myelination
  • oligodendrocyte progenitor cells
  • premature infants

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

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    Vinukonda, G., Hu, F., Mehdizadeh, R., Dohare, P., Kidwai, A., Juneja, A., Naran, V., Kierstead, M., Chawla, R., Kayton, R., & Ballabh, P. (2016). Epidermal growth factor preserves myelin and promotes astrogliosis after intraventricular hemorrhage. Glia, 64(11), 1987-2004. https://doi.org/10.1002/glia.23037