Repositioning flubendazole for spinal cord injury

Chen Guang Yu, Vimala Bondada, Sarbani Ghoshal, Ranjana Singh, Christina K. Pistilli, Kavi Dayaram, Hina Iqbal, Madison Sands, Kate L. Davis, Subarrao Bondada, James W. Geddes

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

We previously reported the serendipitous observation that fenbendazole, a benzimidazole anthelmintic, improved functional and pathological outcomes following thoracic spinal cord contusion injury in mice when administered pre-injury. Fenbendazole is widely used in veterinary medicine. However, it is not approved for human use and it was uncertain if only post-injury administration would offer similar benefits. In the present study we evaluated post-injury administration of a closely related, human anthelmintic drug, flubendazole, using a rat spinal cord contusion injury model. Flubendazole, administered i.p. 5 or 10 mg/kg day, beginning 3 h post-injury and daily thereafter for 2 or 4 weeks, resulted in improved locomotor function after contusion spinal cord injury (SCI) compared with vehicle-treated controls. Histological analysis of spinal cord sections showed that such treatment with flubendazole also reduced lesion volume and improved total tissue sparing, white matter sparing, and gray matter sparing. Flubendazole inhibited the activation of glial fibrillary acidic protein (GFAP); suppressed cyclin B1 expression and Bruton tyrosine kinase activation, markers of B cell activation/proliferation and inflammation; and reduced B cell autoimmune response. Together, these results suggest the use of the benzimidazole anthelmintic flubendazole as a potential therapeutic for SCI.

Original languageEnglish
Pages (from-to)2618-2630
Number of pages13
JournalJournal of Neurotrauma
Volume36
Issue number18
DOIs
StatePublished - Sep 15 2019

Bibliographical note

Publisher Copyright:
© Copyright 2019, Mary Ann Liebert, Inc., publishers 2019.

Keywords

  • b cell-directed therapy
  • cyclin b1
  • flubendazole
  • mild microtubule destabilization
  • traumatic SCI

ASJC Scopus subject areas

  • Clinical Neurology

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