Abstract | OBJECTIVE: Delayed paraplegia after operation on the thoracoabdominal aorta is considered to be related to vulnerability of motor neurons to ischemia. Previous studies have demonstrated the relationship between neuronal vulnerability and endoplasmic reticulum (ER) stress after transient ischemia in the spinal cord. The aim of this study was to investigate whether sodium 4-phenylbutyrate (PBA), a chemical chaperone that reduces the load of mutant or unfolded proteins retained in the ER during cellular stress, can protect against ischemic spinal cord damage. METHODS:
Spinal cord ischemia was induced in rabbits by direct aortic cross-clamping (below the renal artery and above the bifurcation) for 15 minutes at normothermia. Group A (n = 6) was a sham operation control group. In group B (n = 6) and group C (n = 6), vehicle or 15 mg/kg/h of sodium 4-PBA was infused intravenously, respectively, from 30 minutes before the induction of ischemia until 30 minutes after reperfusion. Neurologic function was assessed at 8 hours, and 2 and 7 days after reperfusion with a Tarlov score. Histologic changes were studied with hematoxylin- eosin staining. Immunohistochemistry analysis for ER stress-related molecules, including caspase12 and GRP78 were examined. RESULTS: The mean Tarlov scores were 4.0 in every group at 8 hours, but were 4.0, 2.5, and 3.9 at 2 days; and 4.0, 0.7, and 4.0 at 7 days in groups A, B, and C, respectively. The numbers of intact motor neurons at 7 days after reperfusion were 47.4, 21.5, and 44.9 in groups A, B, and C, respectively. There was no significant difference in terms of viable neurons between groups A and C. Caspase12 and GRP78 immunoreactivities were induced in motor neurons in group B, whereas they were not observed in groups A and C. CONCLUSION:
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Authors | Taketomo Mizukami, Kazumasa Orihashi, Bagus Herlambang, Shinya Takahashi, Makoto Hamaishi, Kenji Okada, Taijiro Sueda |
Journal | Journal of vascular surgery
(J Vasc Surg)
Vol. 52
Issue 6
Pg. 1580-6
(Dec 2010)
ISSN: 1097-6809 [Electronic] United States |
PMID | 20843623
(Publication Type: Journal Article)
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Copyright | Copyright © 2010 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved. |
Chemical References |
- Endoplasmic Reticulum Chaperone BiP
- Heat-Shock Proteins
- Phenylbutyrates
- 4-phenylbutyric acid
- Caspase 12
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Topics |
- Animals
- Aorta, Abdominal
(physiology)
- Aortic Aneurysm
(surgery)
- Apoptosis
- Caspase 12
(metabolism)
- Constriction
- Endoplasmic Reticulum
(drug effects, pathology, physiology)
- Endoplasmic Reticulum Chaperone BiP
- Female
- Heat-Shock Proteins
(metabolism)
- Immunohistochemistry
- Infusions, Intravenous
- Paraparesis
(etiology, pathology, prevention & control)
- Phenylbutyrates
(administration & dosage, therapeutic use)
- Rabbits
- Spinal Cord
(pathology)
- Spinal Cord Ischemia
(etiology, pathology, prevention & control)
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