title: S-Nitrosoglutathione administration ameliorates cauda equina compression injury in rats.
abstract: Lumbar spinal stenosis (LSS) causes ischemia, inflammation, demyelination and results in dysfunction of the cauda equina (CE), leading to pain and locomotor functional deficits. We investigated whether exogenous administration of S-nitrosoglutathione (GSNO), an endogenous redox modulating anti-neuroinflammatory agent, hastens functional recovery in a CE compression (CEC) rat model. CEC was induced in adult female rats by the surgical implantation of two silicone blocks within the epidural spaces of L4-L6 vertebrae. GSNO (50 μg/kg body weight) was administered by gavage 1 h after the injury, and the treatment was continued daily thereafter. GSNO induced change in the pain threshold was evaluated for four days after the compression. Tissue analyses and locomotor function evaluation were carried out at two weeks and four weeks after the CEC respectively. GSNO significantly improved motor function in CEC rats as evidenced by an increased latency on rotarod compared with vehicle-treated CEC rats. CEC induced hyperalgesia was decreased by GSNO. GSNO also increased the expression of VEGF, reduced cellular infiltration (H&E staining) and apoptotic cell death (TUNEL assay), and hampered demyelination (LFB staining and g-ratio). These data demonstrate that administration of GSNO after CEC decreased inflammation, hyperalgesia and cell death leading to improved locomotor function of CEC rats. The therapeutic potential of GSNO observed in the present study with CEC rats suggests that GSNO is a candidate drug to test in LSS patients.
authors.affiliation: Department of Pediatrics Medical University of South Carolina Charleston, SC 29425 USA.
authors.forename: Anandakumar
authors.initials: A
authors.lastname: Shunmugavel
authors.forename: Mushfiquddin
authors.initials: M
authors.lastname: Khan
authors.forename: Marcus M
authors.initials: MM
authors.lastname: Martin
authors.forename: Anne G
authors.initials: AG
authors.lastname: Copay
authors.forename: Brian R
authors.initials: BR
authors.lastname: Subach
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Schuler
authors.forename: Inderjit
authors.initials: I
authors.lastname: Singh
keywords: LSS; VEGF; demyelination; g-ratio; neuroprotection