SCoBIRC FACULTY

Alexander "Sasha" Rabchevsky, Ph.D.

Professor of Physiology
University of Kentucky
Spinal Cord & Brain Injury Research Center (SCoBIRC)

Ph.D., Department of Neuroscience, University of Florida, 1995
Postdoctoral training at University of Paris, XII and University of Kentucky

Curriculum Vitae (pdf)

Dr. Rabchevsky and his lab

Dr. Rabchevsky and his lab

Research Interests

Gene Therapy, Molecular Biology and Pharmacotherapeutics for the Treatment of Spinal Cord Injury

The major focuses of the laboratory are to alleviate both autonomic and/or hind limb locomotor dysfunction following complete transection or incomplete contusion spinal cord injury (SCI) in rats, respectively. In conjunction with precise surgical and histological approaches, paralleled by behavioral, kinematic and physiological assessments, our laboratory is pursuing the following avenues of research.

1)    Employing recombinant viruses to induce site-specific genetic alterations of endogenous cellular responses after SCI in order to elucidate mechanisms contributing to beneficial motor recovery and/or undesirable autonomic pathophysiology.

2)    Using molecular biological and biochemical approaches to test novel mitochondrial-targeted compounds that preserve their integrity and show potent neuroprotective properties that translate into improved functional recovery.

3)    Using radio telemetry of arterial blood pressure (24/7) in animals with complete SCI at or above high thoracic spinal levels to study a condition termed autonomic dysreflexia (AD) that manifests in hypertension that is often triggered by noxious sensations below the injury level.

Mitochondria are the powerhouse of all cells and they are extremely vulnerable to damage following trauma. After reporting, for the first time, the sequential pattern of compromised bioenergetics (damage) of mitochondria after acute contusion SCI, we have since gathered compelling evidence that pharmacological agents which target and maintain mitochondrial function are, indeed, neuroprotective after severe contusion SCI. In particular, when administered within an hour after SCI, they differentially preserve the integrity of both synaptic and non-synaptic mitochondrial populations, assessed one day later. Critically, when delivered more prolong, such preservation is correlated with remarkable long-term behavioral recovery of hind limb locomotion and significant spinal cord tissue sparing.

Autonomic dysreflexia is a potentially life-threatening hypertensive syndrome that often develops after severe high thoracic SCI. While non-painful stimuli can contribute, it is often triggered by noxious stimulation of sensory nerves below the injury that sprout into the injured spinal cord due to elevated expression of nerve growth factor (NGF). Using a rodent model of this pathophysiological condition that is triggered by painful colorectal distension (CRD), we are investigating the contribution of plasticity of both primary afferent axons and propriospinal pathways that are associated with the development of AD. Based on our published findings, we are evaluating the mechanisms by which neuropathic pain medications (gabapentinoids) mitigate the severity of this hypertensive complication after SCI, as well as with muscle spasticity. Moreover, the influence of peripheral inflammation on the severity of CRD-induced AD is being assessed and, ultimately, we seek to correlate such findings with the altered physiological properties of primary sensory neurons and post-ganglionic sympathetic neurons.

Dr. Rabchevsky’s work is currently funded by grants from the National Institutes of Health, the Kentucky Spinal Cord & Head Injury Research Trust (KSCHIRT) and the Craig H. Neilsen Foundation

Selected Publications (from 40 peer-reviewed articles)

Rabchevsky A.G., Patel S.P., Lyttle T.S., Eldahan K.C., O'Dell C.R., Zhang Y., Popovich P.G., Kitzman P.H. and Donohue, K.D. (2012) Effects of gabapentin on muscle spasticity and both induced as well as spontaneous autonomic dysreflexia after complete spinal cord injury. Frontiers Integrative Physiology 3: 329-350. PMID: 22934077

Patel S.P., Sullivan P.G., Lyttle T.S., Magnuson D.S.K. and Rabchevsky A.G. (2012) Acetyl-l-carnitine treatment following spinal cord injury improves mitochondrial function correlated with remarkable tissue sparing and functional recovery. Neuroscience 210: 296–307. PMID: 22445934

Rabchevsky A.G. Patel S.P. and Springer J.E. (2011) Pharmacological interventions for spinal cord injury:  Where do we stand? How might we step forward? Pharmacol. Ther. 132: 15–29. PMID: 21605594

Rabchevsky A.G. and Kitzman P.H. (2011) Latest approaches for the treatment of spasticity and autonomic dysreflexia in chronic spinal cord injury. Neurotherapeutics 8(2): 274-82. PMID: 21384222

Rabchevsky A.G., Patel S.P., Duale H., Lyttle T.S., O'Dell C.R. and Kitzman P.H. (2011) Gabapentin for spasticity & autonomic dysreflexia after severe spinal cord injury. Spinal Cord 49: 99–105. PMID: 20514053

Patel S.P., Sullivan P.G., Lyttle T.S. and Rabchevsky A.G. (2010) Acetyl-L-carnitine ameliorates mitochondrial dysfunction following contusion spinal cord injury. J. Neurochem. 114(1): 291-301. PMID: 20438613

Patel S.P., Pandya J.D., Sullivan P.G. and Rabchevsky A.G. (2009) Effects of mitochondrial uncoupling agent, 2,4-dinitrophenol, or nitroxide antioxidant, tempol, on mitochondrial integrity following acute contusion spinal cord injury. J. Neurosci. Res. 87(1):130-140. PMID: 18709657

Duale H., Hou S.P., Derbenev A.V., Smith B.N. and Rabchevsky A.G. (2009) Spinal cord injury reduces the efficacy of pseudorabies virus labeling of sympathetic preganglionic neurons. J. Neuropathol. Exp. Neurol. 68(2):168-178. PMID: 19151624

Hou S.P., Duale H., Cameron A.A., Abshire S.M., Lyttle T.S. and Rabchevsky A.G. (2008) Plasticity of lumbosacral propriospinal neurons is associated with the development of autonomic dysreflexia after thoracic spinal cord transection. J. Comp. Neurol. 509(4): 382-399. PMID:18512692

Sullivan P.G., Krishnamurthy S., Patel S.P., Pandya J.D. and Rabchevsky A.G. (2007) Temporal characterization of mitochondrial bioenergetics after spinal cord injury. J. Neurotrauma 24(6): 991-999. PMID: 17600515

Rabchevsky A.G. (2006) Segmental organization of spinal reflexes mediating autonomic dysreflexia after spinal cord injury. Prog. Brain Res. 152: Autonomic Dysfunction after Spinal Cord Injury. Weaver L.C. & Polosa C. (eds.), Elsevier B.V.  pp. 265-274. PMID: 16198706

Cameron A.A., Smith G.M., Randall D.C., Brown D.R. and Rabchevsky A.G. (2006) Genetic manipulation of intraspinal plasticity after spinal cord injury alters the severity of autonomic dysreflexia. J. Neurosci. 26(11): 2923-2932. PMID: 16540569

Alexander (Sasha) Rabchevsky

Contact Information

University of Kentucky
Chandler Medical Center
B471 Biomedical & Biological Sciences Research Building
741 S. Limestone Street
Lexington, KY 40536-0509

Tel: (859) 323-0267
Lab: (859) 323-5359
Fax: (859) 257-5737
E-mail: AGRab@uky.edu