title: Fenbendazole improves pathological and functional recovery following traumatic spinal cord injury.
abstract: During a study of spinal cord injury (SCI), mice in our colony were treated with the anthelmintic fenbendazole to treat pinworms detected in other mice not involved in the study. As this was not part of the original experimental design, we subsequently compared pathological and functional outcomes of SCI in female C57BL/6 mice who received fenbendazole (150 ppm, 8 mg/kg body weight/day) for 4 weeks prior to moderate contusive SCI (50 kdyn force) as compared to mice on the same diet without added fenbendazole. The fenbendazole-treated mice exhibited improved locomotor function, determined using the Basso mouse scale, as well as improved tissue sparing following contusive SCI. Fenbendazole may exert protective effects through multiple possible mechanisms, one of which is inhibition of the proliferation of B lymphocytes, thereby reducing antibody responses. Autoantibodies produced following SCI contribute to the axon damage and locomotor deficits. Fenbendazole pretreatment reduced the injury-induced CD45R-positive B cell signal intensity and IgG immunoreactivity at the lesion epicenter 6 weeks after contusive SCI in mice, consistent with a possible effect on the immune response to the injury. Fenbendazole and related benzimadole antihelmintics are FDA approved, exhibit minimal toxicity, and represent a novel group of potential therapeutics targeting secondary mechanisms following SCI.
authors.affiliation: Spinal Cord and Brain Injury Research Center, University of Kentucky College of Medicine, Lexington, KY 40536, USA; Department of Anatomy and Neurobiology, University of Kentucky College of Medicine, Lexington, KY 40536, USA. Electronic address: cyu4@uky.edu.
authors.forename: C G
authors.initials: CG
authors.lastname: Yu
authors.affiliation: Spinal Cord and Brain Injury Research Center, University of Kentucky College of Medicine, Lexington, KY 40536, USA; Department of Anatomy and Neurobiology, University of Kentucky College of Medicine, Lexington, KY 40536, USA. Electronic address: ranjana.singh@uky.edu.
authors.forename: R
authors.initials: R
authors.lastname: Singh
authors.affiliation: Spinal Cord and Brain Injury Research Center, University of Kentucky College of Medicine, Lexington, KY 40536, USA; Department of Anatomy and Neurobiology, University of Kentucky College of Medicine, Lexington, KY 40536, USA. Electronic address: cacrow3@uky.edu.
authors.forename: C
authors.initials: C
authors.lastname: Crowdus
authors.affiliation: Spinal Cord and Brain Injury Research Center, University of Kentucky College of Medicine, Lexington, KY 40536, USA. Electronic address: rkashif79@hotmail.com.
authors.forename: K
authors.initials: K
authors.lastname: Raza
authors.affiliation: Division of Laboratory Animal Resources, University of Kentucky College of Medicine, Lexington, KY 40536, USA. Electronic address: jfkinc2@email.uky.edu.
authors.forename: J
authors.initials: J
authors.lastname: Kincer
authors.affiliation: Spinal Cord and Brain Injury Research Center, University of Kentucky College of Medicine, Lexington, KY 40536, USA; Department of Anatomy and Neurobiology, University of Kentucky College of Medicine, Lexington, KY 40536, USA. Electronic address: jgeddes@uky.edu.
authors.forename: J W
authors.initials: JW
authors.lastname: Geddes
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D005260:Female; D005273:Fenbendazole / Q000627:therapeutic use*; D007074:Immunoglobulin G / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D020127:Recovery of Function / Q000187:drug effects* / Q000502:physiology; D013116:Spinal Cord / Q000473:pathology*; D013119:Spinal Cord Injuries / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors; D015599:Trauma Severity Indices
chemical_list: D007074:Immunoglobulin G; D005273:Fenbendazole; D017493:Leukocyte Common Antigens
keywords: BMS; EC; GLI; ROI; SCI; basso mouse scale; eriochrome cyanine; gray-level-index; locomotor function; pathogenic autoantibody; regions of interest; spinal cord injury; traumatic injury