Fenbendazole improves pathological and functional recovery following traumatic spinal cord injury

Neuroscience. 2014 Jan 3:256:163-9. doi: 10.1016/j.neuroscience.2013.10.039. Epub 2013 Oct 30.

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.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Disease Models, Animal
  • Drug Administration Schedule
  • Female
  • Fenbendazole / therapeutic use*
  • Immunoglobulin G / metabolism
  • Leukocyte Common Antigens / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Recovery of Function / drug effects*
  • Recovery of Function / physiology
  • Spinal Cord / pathology*
  • Spinal Cord Injuries* / drug therapy
  • Spinal Cord Injuries* / pathology
  • Spinal Cord Injuries* / physiopathology
  • Time Factors
  • Trauma Severity Indices

Substances

  • Immunoglobulin G
  • Fenbendazole
  • Leukocyte Common Antigens