Inhibitory effect of MLC901 on axonal demyelination in experimental animals undergoing circumferential lumbal stenosis by increasing transforming growth factor-β1 levels.

Abstract

Study design: Experimental study using circumferential lumbar stenosis (CLS) rat model.

Purpose: To investigate the effect of MLC901 administration on transforming growth factor (TGF)-β1 level and the degree of axonal demyelination in the CLS rat model.

Overview of literature: CLS is common in older adults, causing neuropathic pain that impairs daily functioning. TGF-β1 plays an essential role in nerve regeneration and reducing axonal demyelination in CLS. MLC901, a traditional therapeutic formula, has shown promise in preclinical studies, including modulating proinflammatory cytokines. While MLC901's effect on serum TGF-β1 levels in the CLS rat model has been explored, its impact on tissue TGF-β1 expression remains understudied.

Methods: Rats were randomly allocated into one of six groups: no CLS (baseline), CLS only (pretreatment), short treatment (1 day) with MLC901, short treatment with placebo, longer treatment (7 days) with MLC901, and longer treatment with placebo. The CLS model was induced by laminectomy at the lumbar 5th vertebra, followed by teflon insertion around the dura mater. Serum TGF-β1 levels were measured using enzyme-linked immunosorbent assay. Tissue TGF-β1 expression and the degree of axonal demyelination were assessed by immunohistochemistry and histopathology, respectively.

Results: Long treatment MLC901 group had significantly higher serum TGF-β1 levels than the pretreatment group (p<0.001). Long treatment MLC901 group also exhibited the highest TGF-β1 tissue expression among all treatment groups, including the baseline group (p=0.013). Axonal demyelination was lowest in the long treatment MLC901 group, indicated by the highest number of Schwann cells (p<0.001), the fewest inflammatory cells (except versus baseline) (p=0.001), and the fewest vacuoles (except versus baseline) (p=0.015).

Conclusions: MLC901 can inhibit axonal demyelination in experimental animals undergoing CLS surgery by upregulating TGF-β1 levels. MLC901 has the potential to be used as an adjuvant therapy in CLS surgery.