Bovine Respiratory Syncytial Virus Protects Cotton Rats against
S-Nitrosoglutathione Protects Against Secondary Inflammatory Effects of Acute Spinal Cord Injury in...
-
Upload
marcus-martin -
Category
Documents
-
view
212 -
download
0
Transcript of S-Nitrosoglutathione Protects Against Secondary Inflammatory Effects of Acute Spinal Cord Injury in...
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.