SCoBIRC FACULTY

Alexander "Sasha" Rabchevsky, Ph.D.

Associate 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

Research Interests

Pharmacotherapeutics, Gene Therapy & Molecular Biological Approaches 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, as well as behavioral 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 techniques to characterize novel mitochondrial-targeted pharmacotherapeutics that preserve their integrity and show potent neuroprotective properties, which translates into tissue sparing and remarkable functional recovery following SCI, as measured by kinematic assessments.

3) Studying a condition termed autonomic dysreflexia (AD) that develops after SCI at or above high thoracic levels, which can lead to potentially life-threatening high blood pressure triggered by painful stimulation of sensory nerves below the injury that sprout into the cord due to post-traumatic elevations of growth factors.

Autonomic dysreflexia is a condition that develops after severe high thoracic SCI which can lead to potentially life-threatening hypertension which is often triggered by painful stimulation of sensory nerves below the injury that sprout into the injured spinal cord due to elevated of nerve growth factor (NGF) expression. Using a rodent model of this pathophysiological condition, triggered by painful colorectal distension (CRD, we are investigating the contributions of both primary afferent and propriospinal pathway plasticity to the development of hypertensive autonomic dysreflexia, monitored telemetrically. We are conducting translational pharmaceutical research to test whether blocking excitatory neurotransmission with neuropathic pain medications (gabapentinoids) mitigates the incidence and severity of this secondary complication after SCI, along with muscle spasticity, both of which are triggered by noxious stimulation. We are also investigating the influence of peripheral inflammation on the severity of induced AD, in addition to correlating such findings with the altered physiological properties of primary sensory neurons and post-ganglionic sympathetic neurons.

Mitochondria are the powerhouse of all cells and they are extremely vulnerable to damage following trauma. After establishing the temporal, sequential pattern of compromised bioenergetics (damage) of mitochondria after acute contusion SCI, for the first time, we have 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, particular agents that maintain mitochondrial integrity preserve the integrity of both synaptic and non-synaptic mitochondrial populations, assessed one day later; and this preservation is correlated with remarkable spinal cord tissue sparing and, more importantly, significant long-term behavioral recovery of hind limb locomotion.

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

Recent Publication (from 40 peer-reviewed articles)

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

Zhang X., Patel S.P., McCarthy J.J., Rabchevsky A.G., Goldhamer, D.J. and Esser K.A. (2011) A non-canonical e-box within the myod core enhancer is necessary for circadian expression in skeletal muscle. Nucleic Acids Research 1–12, PMID: 22210883

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

Duale H., Lyttle T.S., Smith B.N. and Rabchevsky A.G. (2010) Noxious colorectal distention in spinalized rats further reduces pseudorabies virus labeling of symapthetic neurons. J. Neurotrauma 27: 1369-1378. PMID: 20528165

Derbenev A.V., Duale H., Rabchevsky A.G. and Smith B.N. (2010) Electrophyiological characteristics of identified kidney-related neurons in adult rat spinal cord slices. Neurosci. Letts. 474(3): 168-172. PMID: 20303390

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