SCoBIRC FACULTYAlexander "Sasha" Rabchevsky, Ph.D.Professor of Physiology Ph.D., Department of Neuroscience, University of Florida, 1995  Dr. Rabchevsky and his lab Research InterestsGene 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
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Contact InformationUniversity of Kentucky Tel: (859) 323-0267 |
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