title: Riluzole blocks perioperative ischemia-reperfusion injury and enhances postdecompression outcomes in cervical spondylotic myelopathy.
abstract: Although surgical decompression is considered the gold standard treatment for cervical spondylotic myelopathy (CSM), a proportion of cases show postoperative decline or continue to exhibit substantial neurological dysfunction. To investigate this further, we first examined data from the prospective multicenter AOSpine North America CSM study, finding that 9.3% of patients exhibited postoperative functional decline (ΔmJOA, ≤-1) and that 44% of patients were left with substantial neurological impairment 6 months postoperatively. Notably, 4% of patients experienced perioperative neurological complications within 20 days after surgery in otherwise uneventful surgeries. To shed light on the mechanisms underlying this phenomenon and to test a combination therapeutic strategy for CSM, we performed surgical decompression in a rat model of CSM, randomizing some animals to also receive the U.S. Food and Drug Administration-approved drug riluzole. Spinal cord blood flow measurements increased after decompression surgery in rats. CSM rats showed a transient postoperative neurological decline akin to that seen in some CSM patients, suggesting that ischemia-reperfusion injury may occur after decompression surgery. Riluzole treatment attenuated oxidative DNA damage in the spinal cord and postoperative decline after decompression surgery. Mechanistic in vitro studies also demonstrated that riluzole preserved mitochondrial function and reduced oxidative damage in neurons. Rats receiving combined decompression surgery and riluzole treatment displayed long-term improvements in forelimb function associated with preservation of cervical motor neurons and corticospinal tracts compared to rats treated with decompression surgery alone.
authors.affiliation: Institute of Medical Sciences, University of Toronto, Toronto, Ontario M5S 1A8, Canada. Division of Genetics and Development, Toronto Western Research Institute, and Spinal Program, Krembil Neuroscience Centre, University Health Network, Toronto, Ontario M5T 2S8, Canada.
authors.forename: Spyridon K
authors.initials: SK
authors.lastname: Karadimas
authors.affiliation: Institute of Medical Sciences, University of Toronto, Toronto, Ontario M5S 1A8, Canada. Division of Genetics and Development, Toronto Western Research Institute, and Spinal Program, Krembil Neuroscience Centre, University Health Network, Toronto, Ontario M5T 2S8, Canada.
authors.forename: Alex M
authors.initials: AM
authors.lastname: Laliberte
authors.affiliation: Institute of Medical Sciences, University of Toronto, Toronto, Ontario M5S 1A8, Canada. Division of Genetics and Development, Toronto Western Research Institute, and Spinal Program, Krembil Neuroscience Centre, University Health Network, Toronto, Ontario M5T 2S8, Canada.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Tetreault
authors.affiliation: Division of Genetics and Development, Toronto Western Research Institute, and Spinal Program, Krembil Neuroscience Centre, University Health Network, Toronto, Ontario M5T 2S8, Canada.
authors.forename: Young Sun
authors.initials: YS
authors.lastname: Chung
authors.affiliation: Department of Neurosurgery, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Arnold
authors.affiliation: Spatio-Temporal Targeting and Amplification of Radiation Response (STTARR) Innovation Centre, Department of Radiation Oncology, University Health Network, Toronto, Ontario M5G 1L7, Canada.
authors.forename: Warren D
authors.initials: WD
authors.lastname: Foltz
authors.affiliation: Institute of Medical Sciences, University of Toronto, Toronto, Ontario M5S 1A8, Canada. Division of Genetics and Development, Toronto Western Research Institute, and Spinal Program, Krembil Neuroscience Centre, University Health Network, Toronto, Ontario M5T 2S8, Canada. Department of Surgery, Division of Neurosurgery and Spinal Program, University of Toronto, Toronto, Ontario M5T 2S8, Canada. michael.fehlings@uhn.ca.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Fehlings
mesh_terms: D000818:Animals; D001369:Axons / Q000473:pathology; D002574:Cervical Vertebrae / Q000473:pathology*; D019299:Decompression, Surgical; D004195:Disease Models, Animal; D006801:Humans; D008279:Magnetic Resonance Imaging; D009046:Motor Neurons / Q000473:pathology; D018696:Neuroprotective Agents / Q000627:therapeutic use; D011446:Prospective Studies; D051381:Rats; D015427:Reperfusion Injury / Q000188:drug therapy*; D019782:Riluzole / Q000627:therapeutic use*; D013116:Spinal Cord / Q000473:pathology; D013118:Spinal Cord Diseases / Q000188:drug therapy* / Q000601:surgery*; D055009:Spondylosis / Q000188:drug therapy* / Q000601:surgery*; D016896:Treatment Outcome
chemical_list: D018696:Neuroprotective Agents; D019782:Riluzole