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.

RhoA/Rho Kinase Mediates Neuronal Death Through Regulating cPLA2 Activation

“…This model has been used reliably in our previous studies [28]. It produces consistent and reliable injuries due to its precise determination of the "0" point of the spinal dorsal surface by a laser sensor and precise determination of displacement parameters of injury.…”

“…The spinal cord contusive injury was performed at the 10 th thoracic (T10) vertebral level with the LISA device at a displacement of 0.5 mm from the dorsal surface of the spinal cord, and a velocity of 1.00 M/Sec as previously described [28]. A total of 4 microinjections of Y27632 (1 microliter 100 µM/injection) were made into the spinal cord immediately after the injury in bilateral and rostrocaudal directions according to the following coordination: 1.0 mm rostrocaudally from the injury epicenter, 0.24 mm laterally from the midline and 0.5 mm ventrally from the dorsal cord surface.…”

A Novel Vertebral Stabilization Method for Producing Contusive Spinal Cord Injury

“…Verify the injury visually by bruising on the spinal cord ( Figure. 5E, arrow) and check the injury parameters provided by the NYU software 12,17 ( Figure 6). 7.…”

“…Therefore, the more joints involved the less stable the spine becomes; 2) the dorsal spinous processes are fragile and cause clamp failure as a result of spinous process fracture or the clamp slipping off of the process; and 3) the spinous processes on these vertebrae are extremely short between the C3 to T1 vertebrae compared to those of the thoracic vertebrae, which makes it difficult using traditional clamps to grasp the spinous processes for stabilizing the cervical spine. 1 , and the Louisville Injury System Apparatus (LISA) 17 , allowing for widespread use in SCI research.…”

Quantification of vascular perfusion in the spinal cord after injury.

“…The dura mater is left intact when using this impactor and the spine is stablized using two pairs of forceps, anchored to adjacent intact vertebre. The IH Impactor delivers a forcedefined impact to the spinal cord and has been shown to be a repeatable and reliable way to mimic human contusion injuries in a rodent model (Zhang, Burke et al 2008). The IH Impactor was set to 150 kilodynes of impact force for all SCI surgeries in this study; this is considered a mild injury.…”