Oxidative stress mediates age-related hypertrophy of ligamentum flavum by inducing inflammation, fibrosis, and apoptosis through activating Akt and MAPK pathways.

The role of oxidative stress in ligamentum flavum (LF) hypertrophy has not been elucidated. We hypothesize that oxidative stress induces inflammatory responses and the subsequent fibrotic processes in LF, via activation of the Akt and MAPK pathways. Specimens of LFs were collected during surgeries for lumbar disc herniation (LDH) or lumbar spinal stenosis (LSS). Part of the LF specimens underwent analyses for ROS, fibrotic markers, and inflammatory mediators, with the remainder minced for cell cultures. The cell cultures were treated with H2O2, after which the cells were lysed and analyzed via western blotting. The specimens of the LSS patients showed increased infiltration of inflammatory cells and were stained positively for MMP-3, MMP-9, vimentin, and fibronectin. The LF of the LSS patients had increased oxidative stress and inflammation compared to that of the LDH patients. In vitro analyses demonstrated that oxidative stress rapidly activated the Akt and MAPK pathways. Inflammatory mediators, iNOS and NF-κB, and fibrotic markers, including TGF-ß, ß-catenin, α-SMA and vimentin, were significantly upregulated after induction of oxidative stress. Oxidative stress activated the intrinsic apoptotic pathway. These findings revealed that oxidative stress is one of the etiological factors of LF hypertrophy, which might provide new insights into treatment approaches.

Expression of hypoxia-inducible factor-1α, vascular endothelial growth factor, and matrix metalloproteinases 1, 3, and 9 in hypertrophied ligamentum flavum.

STUDY DESIGN: Immunohistological study. OBJECTIVE: To elucidate the role of matrix metalloproteinases (MMPs), hypoxia-inducible factor-1α (HIF), and vascular endothelial growth factor (VEGF) in the hypertrophied ligamentum flavum (LF) obtained from patients with lumbar spinal stenosis (LSS). SUMMARY OF BACKGROUND DATA: The most common spinal disorder in the elderly is LSS, which results in part from LF hypertrophy. Although prior histologic and immunochemical studies have been performed in this area, the pathophysiology of loss of elasticity and hypertrophy is not completely understood. METHODS: LF samples of 38 patients with LSS were harvested during spinal decompression. Twelve LF samples obtained from patients with disk herniation and no visible degeneration on preoperative magnetic resonance imaging were obtained as controls. Samples were dehydrated and paraffin embedded. For immunohistochemical determination of VEGF, HIF, and MMPs 1, 3, and 9 expression, slices were stained with VEGF, HIF, and MMP antibody dilution. Neovessel density and number of elastic fibers were counted after Masson-Goldner staining. LF hypertrophy and cross-sectional area (CSA) were measured on T1-weighted magnetic resonance imaging. RESULTS: MMPs 1, 3, 9 and VEGF expression were significantly increased in the hypertrophy group (P<0.05). HIF expression was negative in both groups. Vessel density was increased in the hypertrophy group, although this was not statistically significant. The number of elastic fibres was significantly higher in the control group. In the hypertrophy group, LF thickness was significantly increased, whereas CSA was significantly decreased. There was a statistical correlation between LF thickness, CSA, MMP, and VEGF expression in the hypertrophy group (P<0.05). CONCLUSIONS: LF hypertrophy is accompanied by increased MMPs 1, 3, 9 and VEGF expression. Neovessel density is increased in hypertrophied LF. HIF is not expressed in hypertrophied LF.

Comparison of the effect of 3 different approaches to the lumbar spinal canal on postoperative paraspinal muscle damage.

BACKGROUND: To assess the effect of 3 different surgical approaches on paraspinal muscle atrophy in patients undergoing lumbar back surgery, we compared their pre- and postoperative CT scans and their serum Hb, CRP, and CPK levels. METHODS: The study population consisted of 71 patients who had undergone lumbar back surgery with microscopic posterior decompression without fusion. We examined the effect on paraspinal muscle atrophy of 3 different approaches to the spinal canal. Group 1 (n = 19) underwent unilateral paraspinal dissection from the spinous process with cutting of the spinous process. In group 2 (n = 24), we used modified bilateral decompression via hemilaminectomy, and group 3 (n = 28) was treated by modified bilateral decompression via spinous process splitting. We measured the levels of CPK, Hb, and CRP preoperatively and on the first postoperative day, and compared the preoperative volume of the paraspinal muscle with the volume measured 1 year after the operation. RESULTS: Age, sex, operative time, and CRP and Hb levels were not statistically different among the 3 groups. The postoperative elevation of CPK was significantly lower in groups 2 and 3 than in group 1. Group 3 manifested a significantly lower degree of atrophic changes of the paraspinal muscle than groups 1 and 2. CONCLUSIONS: We found that among the 3 approaches evaluated, modified bilateral decompression via spinous process splitting is less invasive, facilitates preservation of the paraspinal muscle, and is a useful approach to posterior spinal elements resulting in decreased muscle damage.