EGFR inhibition enhances oligodendrocyte precursor cells proliferation and differentiation after contusive spinal cord injury.

Abstract

Traumatic insult to the spinal cord usually leads to severe tissue destruction and cause significant neurological dysfunction to the patient. After spinal cord injury (SCI), neural circuits are disrupted due to massive neuronal and oligodendrocytes death and demyelination. In this study, we aim to investigate the effect of epidermal growth factor receptor (EGFR) inhibition in promoting better functional recovery and tissue repair, and its ability to induce oligodendrocytes precursor cells (OPC) proliferation and differentiation into oligodendrocytes to aid in the reconstruction of neural circuit. Through Basso, Beattie, and Bresnahan (BBB) scoring, we show that mice subjected to contusive SCI recovered better after EGFR inhibitor, PD 168393 (PD), treatment. In addition, examine of spinal cord dorsal-ventral distance shows that PD treated mice exhibit better tissue repair. Immunohistochemistry staining of A2B5 and Myelin basic protein (MBP) show enhance OPC proliferation and differentiation respectively in PD treated mice. Reverse transcription-Polymerase chain reaction (RT-PCR) shows higher level of Myelin oligodendrocyte glycoprotein, MOG, mRNA expression level in PD treated OLN-93 cells. This indicates that EGFR inhibition is able to enhance OPC differentiation into mature, myelinating oligodendrocytes which promote myelination and remyelination. Thus, our findings indicate that EGFR is a potential therapeutic target for SCI.