Abstract | OBJECTIVE: Intrathecal administration of bone marrow stromal cells has been found to produce beneficial effects on ischemia-reperfusion injury to the spinal cord. The blood-spinal cord barrier is critical to maintain spinal cord homeostasis and neurologic function. However, the effects of bone marrow stromal cells on the blood-spinal cord barrier after spinal cord ischemia- reperfusion injury are not well understood. This study investigated the effects and possible mechanisms of bone marrow stromal cells on blood-spinal cord barrier disruption induced by spinal cord ischemia- reperfusion injury. METHODS: This was a prospective animal study conducted at the Central Laboratory of the First Affiliated Hospital, China Medical University. The study used 81 Japanese white rabbits (weight, 1.8-2.6 kg). Spinal cord ischemia- reperfusion injury was induced in rabbits by infrarenal aortic occlusion for 30 minutes. Two days before the injury was induced, bone marrow stromal cells (1 × 10(8) in 0.2-mL phosphate-buffered saline) were transplanted by intrathecal injection. Hind-limb motor function was assessed using Tarlov criteria, and motor neurons in the ventral gray matter were counted by histologic examination. The permeability of the blood-spinal cord barrier was examined using Evans blue (EB) and lanthanum nitrate as vascular tracers. The expression and localization of tight junction protein occludin were assessed by Western blot, real-time polymerase chain reaction, and immunofluorescence analysis. Matrix metalloproteinase-9 (MMP-9) and tumor necrosis factor-α (TNF-α) expression were also measured. RESULTS: Intrathecal transplantation of bone marrow stromal cells minimized the neuromotor dysfunction and histopathologic deficits (P < .01) and attenuated EB extravasation at 4 hours (5.41 ± 0.40 vs 7.94 ± 0.36 μg/g; P < .01) and 24 hours (9.03 ± 0.44 vs 15.77 ± 0.89 μg/g; P < .01) after spinal cord ischemia- reperfusion injury. In addition, bone marrow stromal cells treatment suppressed spinal cord ischemia- reperfusion injury-induced decreases in occludin (P < .01). Finally, bone marrow stromal cells reduced the excessive expression of MMP-9 and TNF-α (P < .01). CONCLUSIONS: Pre-emptive intrathecal transplantation of bone marrow stromal cells stabilized the blood-spinal cord barrier integrity after spinal cord ischemia- reperfusion injury in a rabbit model of transient aortic occlusion. This beneficial effect was partly mediated by inhibition of MMP-9 and TNF-α and represents a potential therapeutic approach to mitigating spinal cord injury after aortic occlusion. CLINICAL RELEVANCE:
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Authors | Bo Fang, He Wang, Xue-Jun Sun, Xiao-Qian Li, Chun-Yu Ai, Wen-Fei Tan, Paul F White, Hong Ma |
Journal | Journal of vascular surgery
(J Vasc Surg)
Vol. 58
Issue 4
Pg. 1043-52
(Oct 2013)
ISSN: 1097-6809 [Electronic] United States |
PMID | 23478501
(Publication Type: Journal Article)
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Copyright | Copyright © 2013 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved. |
Chemical References |
- Occludin
- Tumor Necrosis Factor-alpha
- Matrix Metalloproteinase 9
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Topics |
- Animals
- Bone Marrow Transplantation
- Capillary Permeability
- Cells, Cultured
- Disease Models, Animal
- Hindlimb
- Injections, Spinal
- Matrix Metalloproteinase 9
(metabolism)
- Motor Activity
- Motor Neurons
(pathology)
- Muscle, Skeletal
(innervation)
- Occludin
(metabolism)
- Rabbits
- Reperfusion Injury
(metabolism, pathology, physiopathology, surgery)
- Spinal Cord
(blood supply, metabolism, pathology, physiopathology)
- Stromal Cells
(transplantation)
- Time Factors
- Tumor Necrosis Factor-alpha
(metabolism)
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