title: Spinal cord contusion based on precise vertebral stabilization and tissue displacement measured by combined assessment to discriminate small functional differences.
abstract: Contusive spinal cord injury (SCI) is the most common type of spinal injury seen clinically. Several rat contusion SCI models have been described, and all have strengths and weaknesses with respect to sensitivity, reproducibility, and clinical relevance. We developed the Louisville Injury System Apparatus (LISA), which contains a novel spine-stabilizing device that enables precise and stable spine fixation, and is based on tissue displacement to determine the severity of injury. Injuries graded from mild to moderately severe were produced using 0.2-, 0.4-, 0.6-, 0.8-, 1.0-, and 1.2-mm spinal cord displacement in rats. Basso, Beattie, and Bresnahan (BBB) and Louisville Swim Score (LSS) could not significantly distinguish between 0.2-mm lesion severities, except those of 0.6- and 0.8-mm BBB scores, but could between 0.4-mm injury differences or if the data were grouped (0.2-0.4, 0.6-0.8, and 1.0-1.2). Transcranial magnetic motor evoked potential (tcMMEP) response amplitudes were decreased 10-fold at 0.2-mm displacement, barely detected at 0.4-mm displacement, and absent with greater displacement injuries. In contrast, somatosensory evoked potentials (SSEPs) were recorded at 0.2- and 0.4-mm displacements with normal amplitudes and latencies but were detected at lower amplitudes at 0.6-mm displacement and absent with more severe injuries. Analyzing combined BBB, tcMMEP, and SSEP results enabled statistically significant discrimination between 0.2-, 0.4-, 0.6-, and 0.8-mm displacement injuries but not the more severe injuries. Present data document that the LISA produces reliable and reproducible SCI whose parameters of injury can be adjusted to more accurately reflect clinical SCI. Moreover, multiple outcome measures are necessary to accurately detect small differences in functional deficits and/or recovery. This is of crucial importance when trying to detect functional improvement after therapeutic intervention to treat SCI.
authors.affiliation: Kentucky Spinal Cord Injury Research Center, Department of Neurological Surgery, University of Louisville School of Medicine, Louisville, Kentucky 40202, USA.
authors.forename: Yi Ping
authors.initials: YP
authors.lastname: Zhang
authors.forename: Darlene A
authors.initials: DA
authors.lastname: Burke
authors.forename: Lisa B E
authors.initials: LB
authors.lastname: Shields
authors.forename: Sergey Y
authors.initials: SY
authors.lastname: Chekmenev
authors.forename: Toros
authors.initials: T
authors.lastname: Dincman
authors.forename: Yongjie
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yiyan
authors.initials: Y
authors.lastname: Zheng
authors.forename: Rebecca R
authors.initials: RR
authors.lastname: Smith
authors.forename: Richard L
authors.initials: RL
authors.lastname: Benton
authors.forename: William H
authors.initials: WH
authors.lastname: DeVries
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Hu
authors.forename: David S K
authors.initials: DS
authors.lastname: Magnuson
authors.forename: Scott R
authors.initials: SR
authors.lastname: Whittemore
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Shields
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D004185:Disability Evaluation; D004582:Electronics, Medical; D019054:Evoked Potentials, Motor / Q000502:physiology; D005073:Evoked Potentials, Somatosensory / Q000502:physiology; D016267:External Fixators / Q000592:standards*; D005260:Female; D009431:Neural Conduction / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000473:pathology / Q000503:physiopathology*; D013119:Spinal Cord Injuries / Q000473:pathology / Q000503:physiopathology*; D013131:Spine / Q000033:anatomy & histology / Q000503:physiopathology* / Q000601:surgery; D050781:Transcranial Magnetic Stimulation / Q000379:methods