SCoBIRC FACULTY

Stephen M. Onifer, Ph.D.

Assistant Research Professor 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

Left to Right: Laura Smith-Whitnel, Stephen Onifer, Kashif Raza and Stephanie Albracht

Left: Joshua Eason and Aqsa Qureshi
Right: Oliver Zhang at his research poster for The Math, Science, and Technology Center at Paul Laurence Dunbar High School

Steve Onifer receiving the 2009 "Friend of the Year" Award from the Friends for Michael, Inc. Spinal Cord Injury Organization

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. The dysfunctions are due to the initial mechanical SCI and a complex cascade of processes that lead to progressive death and damage of potentially viable axons and cells as well as impair 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 pharmacological and cellular interventions for their potential to functionally protect and replace damaged spinal cord cells as well as to regenerate axons at the injury site. During recent investigations, we saw that chemical barriers impairing endogenous recovery not only are at the cervical SCI site but they also are at the brainstem target site of spared sensory axons passing through it. Moreover, we observed with electrophysiological and anatomical assessments that degrading chondroitin sulfate proteoglycans in the chemical barrier at the brainstem target site with a bacterial enzyme chondroitinase ABC after cervical SCI led to sprouting of sensory axon collaterals (Figs. 1 & 2).

With funding from the Kentucky Spinal Cord and Head Injury Research Trust, Dr. Onifer and colleagues plan to extend these findings by determining the behavioral consequences of the observed axon collateral sprouting (Fig. 3) and whether combinatorial strategies enhance the therapeutic effects. We also plan to develop combinatorial strategies for the chemical barriers at the injury site to further promote the plasticity of spared 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, Zhang YP, Burke DA, Brooks DL, Decker JA, McClure NJ, Floyd AR, Hall J,Proffitt BL, Shields CB, Magnuson DSK: Adult rat forelimb dysfunction after dorsal cervical spinal cord injury. Experimental Neurology 192: 25-38, 2005.

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.

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, 207:238-247, 2007.

Onifer SM, Rabchevsky AG, Scheff SW: Rat models of traumatic spinal cord injury to assess motor recovery. ILAR Journal, 48:385-395, 2007.

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.

Puckett AH, Nunn CD, Onifer SM: Veterinary care methods for rats and mice in experimental spinal cord injury studies. In: Animal Models of Acute Neurological Injuries, In: Contemporary Neuroscience, J Chen, Z Xu, X-M Xu, J Zhang (eds). The Humana Press Inc., Totowa NJ, 47-60, 2008.

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, 209:426-445, 2008.

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 after damage to sensory afferents in the dorsal columns of the spinal cord. Experimental Neurology, 209:407-416, 2008.

Whitaker CM, Beaumont E, Wells J, Magnuson DSK, Hetman M, Onifer SM: Rolipram attenuates acute oligodendrocyte death in adult rats following a contusive cervical spinal cord injury. Neuroscience Letters, 438:200-204, 2008.

Beaumont E, Whitaker CM, Burke DA, Hetman M, Onifer SM: Effects of rolipram on adult rat oligodendrocytes and functional recovery after contusive cervical spinal cord injury. Neuroscience, 163:985-990, 2009.

Xu XM, Onifer SM: Transplantation-mediated strategies to promote axonal regeneration following spinal cord injury. In: Spinal Cord Injury – Neural Plasticity and Recovery of Respiratory Function, In: Respiratory Physiology & Neurobiology, GC Sieck, CB Mantilla (eds), Elsevier, Amsterdam, 169:171-182, 2009.

Smith GM, Onifer SM: Construction of pathways to promote axon growth within the adult rat central nervous system. Brain Research Bulletin, 84:300-305, 2011.

Onifer SM, Smith GM, Fouad K: Plasticity after spinal cord injury: Relevance to recovery and approaches to facilitate it. Neurotherapeutics, 8:283-293, 2011.

Onifer SM, Zhang O, Whitnel-Smith LK, Raza K, O’Dell CR, Lyttle TS, Rabchevsky AG, Kitzman PH, Burke DA: Horizontal ladder task-specific re-training in adult rats with contusive thoracic spinal cord injury. Restorative Neurology & Neuroscience, 29:275-286, 2011.

Onifer SM: Forelimb functional assessments of rats and mice after cervical spinal cord injury. In: Animal Models of Acute Neurological Injuries II. Injury and Mechanistic Assessments, In: Contemporary Neuroscience, J Chen, Z Xu, X-M Xu, J Zhang (eds). The Humana Press Inc., Totowa NJ, in press, 2012.

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