title: A toll-like receptor 9 antagonist improves bladder function and white matter sparing in spinal cord injury.
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.
authors.affiliation: 1 Department of Neurological Surgery, The Spine Center of New Jersey, The Reynolds Family Spine Laboratory, The State University of New Jersey , Newark, New Jersey.
authors.forename: Brian T
authors.initials: BT
authors.lastname: David
authors.forename: Sujitha
authors.initials: S
authors.lastname: Sampath
authors.forename: Wei
authors.initials: W
authors.lastname: Dong
authors.forename: Adee
authors.initials: A
authors.lastname: Heiman
authors.forename: Courtney E
authors.initials: CE
authors.lastname: Rella
authors.forename: Stella
authors.initials: S
authors.lastname: Elkabes
authors.forename: Robert F
authors.initials: RF
authors.lastname: Heary
mesh_terms: D000818:Animals; D005260:Female; D051379:Mice; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology / Q000627:therapeutic use*; D013119:Spinal Cord Injuries / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D051217:Toll-Like Receptor 9 / Q000037:antagonists & inhibitors*; D001743:Urinary Bladder / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D016055:Urinary Retention / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D066127:White Matter / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology
chemical_list: D009838:Oligodeoxyribonucleotides; D051217:Toll-Like Receptor 9
keywords: CpG ODN; inflammation; pattern recognition receptors; regeneration; traumatic spinal cord injury