Preclinical use of longitudinal MRI for screening the efficacy of S-nitrosoglutathione in treating spinal cord injury.

Abstract

PURPOSE:

To evaluate the therapeutic efficacy of S-nitrosoglutathione (GSNO) in spinal cord injury (SCI) using in vivo MRI in combination with neuorobehavioral testing and postmortem tissue analysis.

MATERIALS AND METHODS:

Sixteen female rats were mildly injured at the vertebral T10 level and randomized into control (n = 8) and GSNO-treatment (n = 8) groups. GSNO was delivered at 0.05 mg/kg dose in saline by means of tail vein at 1 hr postinjury and then given orally on the following days. On postinjury days 1, 3, 7, and 28, the rats were tested behaviorally, then scanned using sagittal T2-weighted MRI for the quantification of lesion, edema, and hemorrhagic regions at the injury site. Excised cords were analyzed using histology and immunohistochemistry.

RESULTS:

Treatment with GSNO was feasible in rats with SCI. On the average, the GSNO group at each scan day 1, 3, 7, and 28 exhibited better functional recovery as indicated by the behavioral performance of 52%, 33%, 19%, and 18%, and had smaller lesions of -4%, -16%, -20%, and -17% compared with the controls, respectively. Edema trend was parallel to the lesion volumes in both groups. Ex vivo data demonstrated that GSNO plays a role in neuronal tissue preservation and sparing.

CONCLUSION:

The data collectively provided the preliminary evidence that the injured rats responded favorably to GSNO treatment. Longitudinal MRI provides critical quantitative information regarding the changes in lesion properties, which helps evaluating the efficacy of an exogenous intervention in SCI.

• Authors: Peter Cheng-te Chou, Anandakumar Shunmugavel, Hanaa El Sayed, Mohamed Mokhtar Desouki, Shaun A Nguyen, Mushfiquddin Khan, Inderjit Singh, Mehmet Bilgen
• Journal: Journal of magnetic resonance imaging : JMRI (J Magn Reson Imaging) Vol. 33 Issue 6 Pg. 1301-11 (Jun 2011) ISSN: 1522-2586 [Electronic] United States
• PMID: 21590998 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2011 Wiley-Liss, Inc.

Chemical References

• Neuroprotective Agents
• S-Nitrosoglutathione

Topics

• Administration, Oral
• Animals
• Drug Evaluation, Preclinical
• Drug Monitoring (methods)
• Edema (pathology)
• Female
• Magnetic Resonance Imaging (methods)
• Nervous System (pathology)
• Neuroprotective Agents (therapeutic use)
• Random Allocation
• Rats
• Rats, Sprague-Dawley
• S-Nitrosoglutathione (therapeutic use)
• Spinal Cord Injuries (drug therapy)
• Time Factors
• Treatment Outcome