88S Proceedings of the NASS 27th Annual Meeting / The Spine Journal 12 (2012) 81S–98S

deficits that can be partially rescued by the neuroprotective agent riluzole.

There exists great interest in translating riluzole for the treatment of SCI,

and this study provides further support for the therapeutic efficacy of rilu-

zole for SCI.

FDA DEVICE/DRUG STATUS: This abstract does not discuss or include

any applicable devices or drugs.

http://dx.doi.org/10.1016/j.spinee.2012.08.245

173. S-Nitrosoglutathione Protects Against Secondary Inflammatory

Effects of Acute Spinal Cord Injury in Rats

Marcus Martin, PhD1, Brian R. Subach, MD, FACS2,

Anandakumar Shunmugavel3, Anne G. Copay, PhD2, Thomas C. Schuler,

MD2, Inderjit Singh, PhD3, Mushfiquddin Khan, PhD3; 1Spinal Research

Foundation, Reston, VA, US; 2Virginia Spine Institute, Reston, VA, US;3Medical University of South Carolina, Charleston, SC, US

BACKGROUND CONTEXT: Spinal Cord Injury (SCI) causes pain and

disability in millions of people each year and is associated with tissue is-

chemia, inflammation, neurodegeneration, and tissue loss. Primary tissue

damage may be the result of acute injury. However, inflammatory media-

tors including cytokines, chemokines and matrix metalloproteinases, can

exacerbate secondary damage and loss of nerve functions. Our recent stud-

ies in rat models of traumatic brain injury and ischemia reperfusion show

that S-nitrosoglutathione (GSNO), a cellular redox modulator, stimulates

motor function recovery and improves neurological function.

PURPOSE: This study investigates the potential application of GSNO

therapy in the treatment of SCI, evaluating its effects on functional recov-

ery, pain threshold, and neuroprotection.

STUDY DESIGN/SETTING: The experiment consisted of three groups:

sham-operated (Sham), vehicle (sterile water)-treated SCI animals (Vehi-

cle), and GSNO-treated SCI animals (GSNO). GSNO (50 mg/kg body

weight) was gavage fed to animals 1 h after surgery and every 24 h thereaf-

ter until the endpoints. GSNO, purchased from world precision Instruments,

Inc, (Sarasota, FL) was dissolved in sterile water and fed to animals via ga-

vage. The administered solution of GSNO was prepared fresh every day.

PATIENT SAMPLE: Female Sprague-Dawley rats (225-250 g), purchased

from Harlan Laboratories (Durham, NC) were housed in the animal facility

at 12 h dark and light cycle.Ambient temperature was maintained at 25�C.The animal procedures for the study were approved by the Institutional An-

imal Care and Use Committee of the Medical University of South Carolina.

Animals were acclimatized for one week before the experiments began.

OUTCOME MEASURES: The animals were tested to determine motor

function, changes in pain threshold and tissue morphology.

METHODS: SCI was induced in adult female rats by surgical implanta-

tion of two silicone blocks in the epidural space of L4-L6 vertebrae. GSNO

(50 mg/kg body weight) was administered 1 h after the injury by gavage,

and the treatment was continued daily thereafter. While the threshold of

pain was evaluated for four days after the injury, biochemical studies

and locomotor function were determined at two weeks and four weeks, re-

spectively, following SCI.

RESULTS: GSNO treatment of SCI significantly improved motor function

as shown by increased rotarod latency compared to vehicle-treated, injured

animals. The treatment also increased pain threshold, reduced cellular in-

filtration (H&E staining), protected against demyelination (LFB staining

and electron microscopic study), and reduced apoptotic cell death (TUNEL

assay). Immunohistochemical studies showed increased expression of vas-

cular VEGF in the cauda equina fibers from GSNO-treated SCI animals.

CONCLUSIONS: The data demonstrates that administration of GSNO af-

ter SCI onset not only protected against tissue damage, increased pain

threshold, enhanced VEGF, and reduced cell death but also improved loco-

motor function. Our results indicate that GSNO warrants further evaluation

as a therapeutic agent in cases of SCI injury in a large mammalian model.

FDA DEVICE/DRUG STATUS: This abstract does not discuss or include

any applicable devices or drugs.

http://dx.doi.org/10.1016/j.spinee.2012.08.246

All referenced figures and tables will be available at the Annual Mee

174. The Effect of Prophylactic Local Epidural Steroid Delivery in

a Spinal Cord Injury Model

Martin Quirno, MD1, Kirk Campbell, MD1, Andrew Yoo, BA1, Jason

M. Cuellar, MD, PhD1, Christian M. Hoelscher, BS1, Pedro A. Ricart-

Hoffiz, MD2, Tate M. Andres, BS1, Thorsten Kirsch, PhD1, Thomas

J. Errico, MD1; 1New York University Hospital for Joint Diseases, New

York, NY, US; 2Westchester Medical Center, Valhalla, NY, US

BACKGROUND CONTEXT: Spinal cord injury (SCI) during high-risk

spinal deformity surgery still occurs despite significant efforts to avoid

it. Current neurophysiological monitoring strategies can only report an in-

jury after it happens, and some injuries fail to be captured. The intravenous

administration of the corticosteroid methylprednisolone (MP) is currently

used to reduce the secondary effects of SCI after primary insult. This pro-

cedure is associated with systemic side-effects and questionable efficacy.

PURPOSE: This study was performed to investigate whether or not a pro-

phylactic injection of the local epidural space with steroids prior to me-

chanical SCI could reduce the long-term consequences of SCI.

STUDY DESIGN/SETTING: An animal study involving adult female

Sprague-Dawley rats and an established SCI model.

METHODS: In adult rats, apreviously described method of incomplete SCI

was utilized by introducing a 2-French embolectomy catheter through a T10

laminotomyand compressing the cord atT8-9by balloon inflation. Therewere

three study groups: the treatment group with prophylactic local epidural injec-

tion ofMPprior to SCI (‘‘SCIþMP’’); the 1st control groupwith pre-operative

normal saline (NS) administered epidurally before SCI (‘‘SCIþNS’’); and, the

2nd control group with epidural injection of MP without SCI (‘‘Steroid On-

ly’’). Ratswere evaluatedweekly for 6weeks by two blinded evaluators utiliz-

ing the Basso-Beattie-Bresnahan (BBB) behavioral scoring system.

RESULTS: The Steroid only group recovered from surgery rapidly without

any behavioral indication of SCI. Significant intragroup differences in mean

BBB score were determined for the SCIþMP and Steroid only groups at 6-

weeks post-SCI (p!0.05), yet this intragroup trend was not observed for the

SCIþNS group. At 6-weeks post-SCI, mean BBB scores were significantly

different between the Steroid Only group and both the SCIþNS group (p!0.001) and SCIþMP group (p!0.05). Mean BBB scores were significantly

higher for the SCIþMP group than for the SCIþNS group at weeks 3, 4,

and 6 (p!0.05), with final mean BBB scores calculated to be 11.8 and

0.5 for the SCIþMP and SCIþNS groups, respectively.

CONCLUSIONS: Rats treated with prophylactic, local epidural MP prior

to mechanical SCI recovered faster and to a significantly greater extent

when compared to those treated with saline only. Furthermore, epidural

MP administration without SCI did not have any observable negative effect

on the health of the rats. Prophylactic, epidural administration of MP has

a greater beneficial effect on rat functional recovery than does intravenous

MP delivered after SCI. We observed 6- and 8-point functional improve-

ments at 3- and 6-weeks after SCI, respectively; in contrast, studies provid-

ing intravenous MP after SCI in the rat have noted a roughly 3-point

improvement at 4 weeks after injury. Prophylactic treatment of high-risk

spinal deformity surgery patients with a high concentration of epidural

or intrathecal MP may have potential to mitigate the severity of SCI. This

possibility deserves further investigation in animal and human subjects.

FDA DEVICE/DRUG STATUS: This abstract does not discuss or include

any applicable devices or drugs.

http://dx.doi.org/10.1016/j.spinee.2012.08.247

175. The Sodium Channel/Glutamate Blocker Riluzole is

Complementary to Decompression in a Preclinical Experimental

Model of Cervical Spondylotic Myelopathy: Implications for

Translational Clinical Application

Spyridon Karadimas1, Michael G. Fehlings, MD, PhD, FRCSC2; 1Toronto,

ON, Canada; 2Toronto Western Hospital, Toronto, ON, Canada

BACKGROUND CONTEXT: Authors: Spyridon K. Karadimas, Eun Su

Moon, Michael G. Fehlings While successful surgical intervention can ar-

rest the progression of cervical spondylotic myelopathy (CSM), most

ting and will be included with the post-meeting online content.