Dose-dependent regulation of cell proliferation and collagen degradation by estradiol on ligamentum flavum.

BACKGROUND: Estradiol plays an important role in the regulation of collagen metabolism. Deficiency of estradiol has been reported to be associated with the degeneration of many connective tissues. However, the association of estradiol and hypertrophy of the ligamentum flavum was seldom explored. Therefore, we studied the effects of estradiol on cultured cells from the ligamentum flavum. METHODS: Primary cultures of human ligamentum flavum cells obtained from surgical specimens of 14 patients undergoing spinal surgery were used to investigate the effect of estradiol on cell proliferation and the expression of collagen, elastin, and matrix metalloproteinases. Downstream pathways of estrogen receptor underlying the regulation of metalloproteinases were also investigated. RESULTS: In our study, we revealed the existence of estrogen receptors on both female and male ligamentum flavum cells with a gender difference. 17ß-estradiol increased early (24 hours) proliferation of ligamentum flavum cells in a dose dependent manner and the effect could not be seen when the cell density increased. Estradiol with a concentration of 10(-9) M decreased collagen levels and increased the expression of MMP-13. Adding an antagonist of PI3K downstream pathway could reverse the expression of MMP-13 caused by estradiol. CONCLUSIONS: The results implied estradiol regulated the expression of MMP-13 via PI3K pathway and contributed to the homeostasis of extracellular matrix in the ligamentum flavum.

Integration of multiple prognostic predictors in a porcine spinal cord injury model: A further step closer to reality.

Introduction: Spinal cord injury (SCI) is a devastating neurological disorder with an enormous impact on individual's life and society. A reliable and reproducible animal model of SCI is crucial to have a deeper understanding of SCI. We have developed a large-animal model of spinal cord compression injury (SCI) with integration of multiple prognostic factors that would have applications in humans. Methods: Fourteen human-like sized pigs underwent compression at T8 by implantation of an inflatable balloon catheter. In addition to basic neurophysiological recording of somatosensory and motor evoked potentials, we introduced spine-to-spine evoked spinal cord potentials (SP-EPs) by direct stimulation and measured them just above and below the affected segment. A novel intraspinal pressure monitoring technique was utilized to measure the actual pressure on the cord. The gait and spinal MRI findings were assessed in each animal postoperatively to quantify the severity of injury. Results: We found a strong negative correlation between the intensity of pressure applied to the spinal cord and the functional outcome (P < 0.0001). SP-EPs showed high sensitivity for real time monitoring of intraoperative cord damage. On MRI, the ratio of the high-intensity area to the cross-sectional of the cord was a good predictor of recovery (P < 0.0001). Conclusion: Our balloon compression SCI model is reliable, predictable, and easy to implement. By integrating SP-EPs, cord pressure, and findings on MRI, we can build a real-time warning and prediction system for early detection of impending or iatrogenic SCI and improve outcomes.

Sarcoma of the cervical spine after radiation treatment for thyroid cancer.

STUDY DESIGN: Case report. OBJECTIVE: We report a rare case of postradiation sarcoma of the cervical spine 30 years after treatment for thyroid cancer. SUMMARY OF BACKGROUND DATA: The reported case is a 66-year-old man with a history of thyroid cancer treated with surgery and radiotherapy at the age of 36 years. He was disease-free for 30 years, but then developed left upper limb weakness and numbness. Magnetic resonance imaging showed a homogeneously enhanced mass lesion with cystic parts involving the C4 vertebral body and occupying the left side of the spinal canal with extension to the paraspinal space through the neural foramen. METHODS: Using staged posterior and anterior approaches, gross total tumor excision, C4 corpectomy, and spinal fusion were achieved. RESULTS: The histologic diagnosis revealed sarcoma that was immunoreactive to vimentin and focally to S100 and O13 antibodies. Radiation-induced sarcoma should be suspected in patients who have received radiation treatment previously and present with new neurologic symptoms and signs in the irradiated area. The patient's muscle power returned to 5/5, except for the left upper extremity, which reached 2/5; he was free from recurring symptoms during the follow-up period. CONCLUSION: Because of advancements in diagnostic techniques and therapeutic methods, more patients survive primary cancer, and therefore an increase in the number of cases of postradiation sarcoma is expected. Postradiation sarcomas have extremely long latent periods, and one should therefore always keep in mind such a complication of previous radiation treatment.