Alpha Omega Alpha Honor Medical Society

2010 Research Abstract

Early Disregulation of Schwann Cell Phenotype is Associated with Age-Dependent Decline in Functional Recovery Following Nerve Injury

Investigator: Wayne Chen, Wake Forest University Health Sciences School of Medicine
Authors: Wayne A. Chen, BS; Jonathan C. Barnwell, MD; Casey N. Northam, BS; Zhongyu Li, MD, PhD
Mentors: Zhongyu J. Li, MD, PhD, and Jonathan C. Barnwell, MD, Department of Orthopaedic Surgery, Wake Forest University School of Medicine

Schwann cells are integral to the regenerative capacity of the peripheral nervous system (PNS) and are responsible for remyelination following nerve injury. Although the neuroregenerative potential of the PNS declines following adolescence, the mechanisms underlying this age-dependent decline are poorly understood. We hypothesize that Schwann cell myelinating regulatory factors are downregulated by early adulthood, resulting in poor functional recovery following nerve injury. Sciatic nerve crush injury was performed in young (2 mo.) and adult (12 mo.) rats obtained from the National Institute on Aging. Nerve segments distal and contralateral to the lesion were harvested at 1, 3, and 7 days post-injury. Protein expression of dedifferentiating regulatory factors, Notch and c-Jun, and the remyelinating regulatory factor, Krox-20, was quantified by Western blot. Functional recovery was assessed over an 8 week period by gait analysis using the Sciatic Functional Index (SFI) and nerve conduction studies of compound motor action potentials (CMAP). No significant differences were observed in Schwann cell myelinating regulatory factors. However, preliminary findings suggest that adult rats exhibited delayed onset of dedifferentiating regulatory factors, Notch and c-Jun. This phenotypic delay corresponds to the delayed functional recovery seen in adult rats. Significant differences in SFI were observed at 3, 4, 5, and 7 weeks post-injury (p<0.001). A significant difference was detected in CMAP area between young (1.159 ± 0.148) and adult (0.505 ± 0.0378) rats (p=0.017). No significant difference in CMAP amplitude was detected (p=0.056). The ability to signal dedifferentiation from a myelinating Schwann cell phenotype was delayed in adult rats following nerve injury. These results support our hypothesis that Schwann cell dysfunction is evident in the period immediately following nerve injury in adult rats. Poor neurorecovery is expected in ages much earlier than senescence and is correlated with impaired functional recovery in this animal model. Identification of signals upstream to these regulatory factors may provide insights into future therapies targeting the poor neuroregenerative potential seen in the adult patient population.

Supported by the American Society for Surgery of the Hand, Wake Forest University Health Sciences, Alpha Omega Alpha Carolyn L. Kuckein Student Research Fellowship.

Updated on February 17, 2011.

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