title: Inhibition of Epidermal Growth Factor Receptor Improves Myelination and Attenuates Tissue Damage of Spinal Cord Injury.
abstract: Preventing demyelination and promoting remyelination of denuded axons are promising therapeutic strategies for spinal cord injury (SCI). Epidermal growth factor receptor (EGFR) inhibition was reported to benefit the neural functional recovery and the axon regeneration after SCI. However, its role in de- and remyelination of axons in injured spinal cord is unclear. In the present study, we evaluated the effects of EGFR inhibitor, PD168393 (PD), on the myelination in mouse contusive SCI model. We found that expression of myelin basic protein (MBP) in the injured spinal cords of PD treated mice was remarkably elevated. The density of glial precursor cells and oligodendrocytes (OLs) was increased and the cell apoptosis in lesions was attenuated after PD168393 treatment. Moreover, PD168393 treatment reduced both the numbers of OX42 + microglial cells and glial fibrillary acidic protein + astrocytes in damaged area of spinal cords. We thus conclude that the therapeutic effects of EGFR inhibition after SCI involves facilitating remyelination of the injured spinal cord, increasing of oligodendrocyte precursor cells and OLs, as well as suppressing the activation of astrocytes and microglia/macrophages.
authors.affiliation: School of Life Science and Technology, Xinxiang Medical University, Jinsui Road, Xinxiang, 453003, Henan, China.|Brain Research Center, Faculty of Medicine, University of British Columbia, Vancouver, BC, V6T 2B5, Canada.
authors.forename: Si
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 201108, China.
authors.forename: Peijun
authors.initials: P
authors.lastname: Ju
authors.affiliation: School of Biological Sciences, Nanyang Technological University, Singapore, Singapore.
authors.forename: Editha
authors.initials: E
authors.lastname: Tjandra
authors.affiliation: Cytogenetics Laboratory, Singapore General Hospital, Singapore, Singapore.
authors.forename: Yeeshan
authors.initials: Y
authors.lastname: Yeap
authors.affiliation: School of Biological Sciences, Nanyang Technological University, Singapore, Singapore.
authors.forename: Hamed
authors.initials: H
authors.lastname: Owlanj
authors.affiliation: School of Life Science and Technology, Xinxiang Medical University, Jinsui Road, Xinxiang, 453003, Henan, China. 123066@xxmu.edu.cn.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Feng
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects; D001369:Axons / Q000187:drug effects; D004195:Disease Models, Animal; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D051379:Mice; D009186:Myelin Sheath / Q000187:drug effects*; D009457:Neuroglia / Q000187:drug effects; D009836:Oligodendroglia / Q000187:drug effects; D011799:Quinazolines / Q000494:pharmacology; D020127:Recovery of Function / Q000187:drug effects* / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: C509204:PD168393; D011799:Quinazolines; D066246:ErbB Receptors
keywords: EGFR inhibition; Remyelination; Spinal cord injury