Local Down-regulation of Myelin-associated Glycoprotein Permits Axonal Sprouting in a Model for Carpal Tunnel Syndrome

*Rummler, LS; *Palispis, WA; *Truong, LN; *Chao, T; *Rowshan, K; +*Gupta, RG +*University of California Irvine, Irvine, CA [email protected] INTRODUCTION: Chronic nerve compression (CNC) injuries, such as carpal tunnel syndrome, are common orthopaedic conditions. Until recently, little has been known about the cellular and molecular changes after CNC injury. Acute nerve injuries, like axotomy and crush, trigger a degenerative pathway in the neurons known as Wallerian degeneration. Early studies of CNC injury found a gradual decrease in axonal number, which led to the assumption that CNC injury induces a mild form of Wallerian degeneration. However, more rigorous investigation led us to postulate that Schwann cells may actually mediate CNC injury-related pathology. Early studies revealed increases in the number of unmyelinated axons at the site of compression, suggesting an axonal sprouting response [1, 2]. During acute axonal injury, axons can sprout new nerve endings to reconnect with damaged or denervated neurons. However, since we were unable to find any evidence of axonal injury, we hypothesized that the axonal sprouting may actually be triggered by Schwann cells. Multiple studies have provided evidence that Schwann cell-derived molecules, such as myelin-associated glycoprotein (MAG), inhibit axonal growth and sprouting. Recent in-vitro data has demonstrated that cultured Schwann cells down-regulate MAG mRNA and protein in response to direct mechanical stimulation [3]. As such, we hypothesized that Schwann cells may locally down-regulate their expression of MAG in the early stages of CNC injury and that this decrease in MAG expression may facilitate axonal sprouting.