Epidermal growth factor receptor inhibition enhances locomotor recovery and neurogenesis in mouse spinal cord injury.

Abstract

Spinal cord injury (SCI) often leads to severe loss of axonal tracts in Central Nervous System (CNS), impairing sensory and motor signals transmission between brain and remainder of the body, which causes long-term physiological dysfunctions in SCI patients. Due to the limited self-regenerative ability in adult CNS, axonal regeneration after SCI is very minimal. Recently, inhibition of Epidermal Growth Factor Receptor (EGFR) was shown to induce axonal regeneration both in vitro and in vivo. Here, we show that EGFR inhibitor can effectively promote axonal regeneration and remyelination, leading to enhanced locomotor recovery in contusion SCI mice. However, the underlying mechanisms of these positive outcomes are unknown. In addition, we found that EGFR inhibitor can possibly drive a population of CNS multipotent cells, NG2 cells, towards neuronal fate both in vitro and in vivo. NG2 cells have been shown to accumulate at lesion site soon after SCI. We proposed that the enhanced axonal regeneration event in EGFR inhibitor-treated SCI mice could possibly be contributed by increased neuronal differentiation of NG2 cells at SCI lesion site. Therefore, targeting the novel link between EGFR inhibition and NG2 cells may be a new therapeutic strategy for SCI treatment.