title: A reassessment of a classic neuroprotective combination therapy for spinal cord injured rats: LPS/pregnenolone/indomethacin.
abstract: These experiments were completed as part of an NIH-NINDS contract entitled "Facilities of Research Excellence-Spinal Cord Injury (FORE-SCI)-Replication". Our goal was to replicate data from a paper published by Dr. Lloyd Guth and colleagues in which combined injections of lipopolysaccharide, indomethacin and pregnenolone (referred to herein as LIP therapy) conferred marked neuroprotection in a pre-clinical model of spinal cord injury (SCI). Specifically, post-injury injection of the combination LIP therapy was found to significantly reduce tissue damage at/nearby the site of injury and significantly improve recovery of locomotor function. In this report, we confirm the primary observations made by Guth et al., however, the effects of LIP treatment were modest. Specifically, LIP treatment improved myelin and axon sparing, axonal sprouting while reducing lesion cavitation. However, spontaneous recovery of locomotion, as assessed using historical (Tarlov scoring) and more current rating scales (i.e., BBB scoring), was not affected by LIP treatment. Instead, more refined parameters of functional recovery (paw placement accuracy during grid walk) revealed a significant effect of treatment. Possible explanations for the neuroprotective effects of LIP therapy are described along with reasons why the magnitude of neuroprotection may have differed between this study and that of Guth and colleagues.
authors.affiliation: Center for Brain and Spinal Cord Repair, The Ohio State University College of Medicine, Columbus, OH, USA. phillip.popovich@osumc.edu
authors.forename: Phillip G
authors.initials: PG
authors.lastname: Popovich
authors.forename: C Amy
authors.initials: CA
authors.lastname: Tovar
authors.forename: Ping
authors.initials: P
authors.lastname: Wei
authors.forename: Lesley
authors.initials: L
authors.lastname: Fisher
authors.forename: Lyn B
authors.initials: LB
authors.lastname: Jakeman
authors.forename: D Michele
authors.initials: DM
authors.lastname: Basso
mesh_terms: D000818:Animals; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004359:Drug Therapy, Combination; D005260:Female; D007213:Indomethacin / Q000008:administration & dosage*; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D010865:Pilot Projects; D011284:Pregnenolone / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D013119:Spinal Cord Injuries / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*
chemical_list: D008070:Lipopolysaccharides; D018696:Neuroprotective Agents; D011284:Pregnenolone; D007213:Indomethacin