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Hypertrophy of the lumbar ligamentum flavum is associated with inflammation-related TGF-β expression

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Abstract

Background

Despite the significance of hypertrophy of the ligamentum flavum (HLF) in the disease progress of neurogenic claudication, the cellular mechanisms underlying the gradual fibrotic thickening of the ligamentum flavum remain poorly understood. The aim of our study was to get insight into the contribution of inflammatory mechanisms to the development of hypertrophy.

Methods

Specimens of hypertrophied ligamenta flava were obtained at surgery from 20 patients with acquired lumbar osteoligamentous spinal canal stenosis from the central part of the ligament. Paraffin sections were stained with hematoxylin and eosin and Elastica van Gieson to evaluate extracellular matrix architecture, and immunohistochemistry was performed to characterize the inflammatory reaction and the sources of transforming growth factor beta (TGF-β) expression. Sections of normal ligamenta flava obtained from corresponding anatomical sites and stained in parallel served as a control.

Results

HLF was characterized by a considerable distortion of the elastic matrix and fibrotic transformation by extracellular collagen deposition. All specimens showed highly inflammatory cellular infiltrates confined to regions exhibiting marked degeneration of the elastic matrix composed mainly of macrophages, scattered T lymphocytes, and neovascularization, thus representing a chronic inflammation. Surprisingly, macrophages as well as vascular endothelial cells but not fibroblasts showed a strong expression of TGF-β, a strong inducer of extracellular collagen deposition.

Conclusions

Macrophages were identified as a major cellular source of TGF-β in advanced HLF and may perpetuate further hypertrophy. This finding suggests that modulating the immune response locally or systemically could prove to be effective for impeding the disease progress.

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Author notes

  1. Mario Löhr, Jin Yul Lee & Ralf-Ingo Ernestus

    Present address: Department of Neurosurgery, University of Wuerzburg, Josef-Schneider-Strasse 11, 97080, Wuerzburg, Germany

  2. Werner Stenzel

    Present address: Department of Neuropathology, Charité - Universitätsmedizin, Charitéplatz 1/Virchowweg 15, 10117, Berlin, Germany

Authors and Affiliations

  1. Department of General Neurosurgery, University Hospital of Cologne, Kerpener Strasse 62, 50924, Cologne, Germany

    Mario Löhr, Jürgen Anton Hampl, Jin Yul Lee & Ralf-Ingo Ernestus

  2. Department of Neuropathology, University Hospital of Cologne, Kerpener Strasse 62, 50924, Cologne, Germany

    Martina Deckert & Werner Stenzel

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  1. Mario Löhr
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Correspondence to Mario Löhr.

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Löhr, M., Hampl, J.A., Lee, J.Y. et al. Hypertrophy of the lumbar ligamentum flavum is associated with inflammation-related TGF-β expression. Acta Neurochir 153, 134–141 (2011). https://doi.org/10.1007/s00701-010-0839-7

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  • DOI: https://doi.org/10.1007/s00701-010-0839-7

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