A toll-like receptor 9 antagonist improves bladder function and white matter sparing in spinal cord injury

Brian T. David, Sujitha Sampath, Wei Dong, Adee Heiman, Courtney E. Rella, Stella Elkabes, Robert F. Heary

Research output: Contribution to journalArticlepeer-review

Abstract

Spinal cord injury (SCI) affects motor, sensory, and autonomic functions. As current therapies do not adequately alleviate functional deficits, the development of new and more effective approaches is of critical importance. Our earlier investigations indicated that intrathecal administration of a toll-like receptor 9 (TLR9) antagonist, cytidine-phosphate-guanosine oligodeoxynucleotide 2088 (CpG ODN 2088), to mice sustaining a severe, mid-thoracic contusion injury diminished neuropathic pain but did not alter locomotor deficits. These changes were paralleled by a decrease in the pro-inflammatory response at the injury epicenter. Using the same SCI paradigm and treatment regimen, the current studies investigated the effects of the TLR9 antagonist on bladder function. We report that the TLR9 antagonist decreases SCI-elicited urinary retention and ameliorates bladder morphopathology without affecting kidney function. A significant improvement in white matter sparing was also observed, most likely due to alterations in the inflammatory milieu. These findings indicate that the TLR9 antagonist has beneficial effects not only in reducing sensory deficits, but also on bladder dysfunction and tissue preservation. Thus, modulation of innate immune receptor signaling in the spinal cord can impact the effects of SCI.

Original languageAmerican English
Pages (from-to)1800-1806
Number of pages7
JournalJournal of neurotrauma
Volume31
Issue number21
DOIs
StatePublished - Nov 1 2014

ASJC Scopus subject areas

  • Clinical Neurology

Keywords

  • CpG ODN
  • inflammation
  • pattern recognition receptors
  • regeneration
  • traumatic spinal cord injury

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