SCoBIRC FACULTY

Stephen M. Onifer, Ph.D.

Assistant Professor
Spinal Cord and Brain Injury Research Center, Department of Anatomy and Neurobiology

Ph.D., Indiana University School of Medicine (1991). Postdoctoral training at The Miami Project to Cure Paralysis, University of Miami School of Medicine.

Research Interests

Pharmacological Approaches to Neuroprotection and Plasticity after Spinal Cord Injury
The devastating motor, sensory, and autonomic dysfunctions occurring after traumatic spinal cord injury (SCI) produce long-term physical, emotional, and financial burdens to the survivors as well as to their families and friends. Administration of high doses of the glucocorticoid methylprednisolone after the SCI is the only clinically approved treatment. Thus, cures for SCI and alleviating its burdens are under experimental investigation. The dysfunctions are due to the initial mechanical SCI and a complex cascade of processes that lead to the progressive death and damage of potentially viable axons and cells as well as impairs endogenous recovery mechanisms. Using models of cervical, where most human injuries occur, and thoracic SCI combined with electrophysiological and behavioral assessments of motor and sensory functions plus histology, Dr. Onifer and colleagues have evaluated interventions for their potential to regenerate axons and to replace cells at the injury site so as to improve upper and lower limbs functions. During recent investigations, they found that oligodendrocytes, the cells which myelinate axons to aid in their neurotransmission, can be preserved after injury by administering rolipram which inhibits phosphodiesterase type 4 degradation of cAMP and alters the inflammatory processes of the secondary injury cascade. Associated with the neuroprotection were improvements in lower limb functions. They also saw that chemical barriers impairing endogenous recovery not only are at the injury site but also at the target site of axons passing through it. Moreover, they observed that degrading chondroitin sulfate proteoglycans in the chemical barrier at a target site with an enzyme chondroitinase ABC led to functional sprouting of axon collaterals. Dr. Onifer and colleagues plan to extend these findings by optimizing and further developing the neuroprotection as well as elucidating the mechanisms by which this occurs. Additionally, they plan to optimize and develop strategies for degrading the chemical barriers at both the injury and target sites to promote plasticity of functional axons.

Representative Publications

Onifer SM, Rodríquez JF, Santiago DI, Benitez JC, Kim DT, Brunschwig J-P, Pacheco JT, Perrone JV, Llorente O, Martinez-Arizala A: Cervical spinal cord injury in the adult rat: Assessment of forelimb dysfunction. Restorative Neurology and Neuroscience 11:211-223, 1997.

Onifer SM, Magnuson DSK, Shields CB, Whittemore SR: Grafting into the injured spinal cord to restore locomotion: Two decades of promise yet to be fulfilled. Neuroscience News, 3:50-50, 2000.

Loy DN, Crawford CH, Darnall JB, Burke DA, Onifer SM, Whittemore SR: Temporal progression of angiogenesis and basal lamina deposition after contusive spinal cord injury in the adult rat. Journal of Comparative Neurology 445:308-324, 2002.

Loy DN, Magnuson DSK, Zhang YP, Onifer SM, Mills MD, Cao Q-L, Darnall JB, Fajardo LC, Burke DA, Whittemore SR: Functional redundancy of ventral spinal locomotor pathways. Journal of Neuroscience 22:315-323, 2002.

Massey JM, Hubscher CH, Wagoner MR, Decker JA, Amps J, Silver J, Onifer SM: Chondroitinase ABC digestion of the perineuronal net promotes functional collateral sprouting in the cuneate nucleus following cervical spinal cord injury. Journal of Neuroscience, 26:4406-4414, 2006.

Cottrell BL, Perez-Abadia G, Onifer SM, Magnuson DS, Burke DA, Grossi FV, Francois CG, Barker JH, Maldonado C: Neuroregeneration in composite tissue allografts: Effect of low dose FK506 and mycophenolate mofetil immunotherapy. Plastic and Reconstructive Surgery, 118:615-623, 2006.

Willson CA, Foster RD, Onifer SM, Whittemore SR, Miranda JD: EphB3 receptor and its ligand expression in the adult rat brain. Journal of Molecular Histology, 37:369-380, 2006.

Reed WR, Shum-Siu A, Onifer SM, Magnuson DSK: Inter-enlargement pathways in the ventrolateral funiculus of the adult rat spinal cord. Neuroscience, 142:1195-1207, 2006.

Beaumont E, Onifer SM, Reed WR, Magnuson DSK: Magnetically-evoked inter-enlargement response: An assessment of ascending propriospinal fibers following spinal cord injury. Experimental Neurology, 201:428-440, 2006.

Burke DA, Magnuson DSK, Nunn CD, Fentress KG, Wilson ML, Shum-Siu AH, Moore MC, Turner LE, King WW, Onifer SM: Use of environmentally enriched housing for rats with spinal cord injury: The need for standardization. Journal of the American Association for Laboratory Animal Science, 46:35-42, 2007.

Massey JM, Amps J, Viapiano MS, Matthews RT, Wagoner MR, Whitaker CM, Alilain W, Yonkof A, Khalyfa A, Cooper NGF, Silver J, Onifer SM: Increased chondroitin sulfate proteoglycan expression in denervated brainstem targets following spinal cord injury creates a barrier to axonal regeneration overcome by chondroitinase ABC and neurotrophin-3. Experimental Neurology, in press, 2007.

Onifer SM, Rabchevsky AG, Scheff SW: Rat models of traumatic spinal cord injury to assess motor recovery. ILAR Journal, in press, 2007.

Titsworth WL, Onifer SM, Liu N, Xu X-M: Focal phospholipases A2 group III injections induce cervical white matter injury and functional deficits with delayed recovery concomitant with Schwann cell remyelination. Experimental Neurology, in press, 2007.

Kaas JH, Qi H-X, Burish M, Gharbawie O, Onifer SM, Massey JM: Cortical and subcortical plasticity in the brains of humans, primates, and rats and primates after damage to sensory afferents in the dorsal columns of the spinal cord. Experimental Neurology, in press, 2007.

Onifer SM, Nunn CD, Decker JA, Payne BN, Wagoner, MR, Puckett AH, Massey JM, Armstrong J, Kaddumi EG, Fentress KG, Wells MJ, Calloway CC, Schnell JT, Whitaker CM, Burke DA, Hubscher CH: Loss and spontaneous recovery of forelimb evoked potentials in both the adult rat cuneate nucleus and somatosensory cortex following contusive cervical spinal cord injury. Experimental Neurology, in press, 2007.