A Consistent, Quantifiable, and Graded Rat Lumbosacral Spinal Cord Injury Model

Abstract

The purpose of this study is to develop a rat lumbosacral spinal cord injury (SCI) model that causes consistent motoneuronal loss and behavior deficits. Most SCI models focus on the thoracic or cervical spinal cord. Lumbosacral SCI accounts for about one third of human SCI but no standardized lumbosacral model is available for evaluating therapies. Twenty-six adult female Sprague-Dawley rats were randomized to three groups: sham (n=9), 25 mm (n=8), and 50 mm (n=9). Sham rats had laminectomy only, while 25 mm and 50 mm rats were injured by dropping a 10 g rod from a height of 25 mm or 50 mm, respectively, onto the L4-5 spinal cord at the T13/L1 vertebral junction. We measured footprint length (FL), toe spreading (TS), intermediate toe spreading (ITS), and sciatic function index (SFI) from walking footprints, and static toe spreading (STS), static intermediate toe spreading (SITS), and static sciatic index (SSI) from standing footprints. At six weeks, we assessed neuronal and white matter loss, quantified axons, diameter, and myelin thickness in the peroneal and tibial nerves, and measured cross-sectional areas of tibialis anterior and gastrocnemius muscle fibers. The result shows that peroneal and tibial motoneurons were respectively distributed in 4.71 mm and 5.01 mm columns in the spinal cord. Dropping a 10-g weight from 25 mm or 50 mm caused 1.5 mm or 3.75 mm gaps in peroneal and tibial motoneuronal columns, respectively, and increased spinal cord white matter loss. Fifty millimeter contusions significantly increased FL and reduced TS, ITS, STS, SITS, SFI, and SSI more than 25 mm contusions, and resulted in smaller axon and myelinated axon diameters in tibial and peroneal nerves and greater atrophy of gastrocnemius and anterior tibialis muscles, than 25 mm contusions. This model of lumbosacral SCI produces consistent and graded loss of white matter, motoneuronal loss, peripheral nerve axonal changes, and anterior tibialis and gastrocnemius muscles atrophy in rats.

Neuromodulatory effects of repetitive transcranial magnetic stimulation on neural plasticity and motor functions in rats with an incomplete spinal cord injury: A preliminary study

“…BBB might not be applicable to determine the locomotor function for an injury at the thoracic level. One study that created a contusion injury in the lumbosacral region revealed that no behavioral changes could be assessed by BBB scores [ 62 ]. Further, the BBB score focuses on joint movement, weight-bearing, coordination between limbs, postural view, and the positions of the tail and feet [ 43 , 61 ].…”

A novel technique to develop thoracic spinal laminectomy and a methodology to assess the functionality and welfare of the contusion spinal cord injury (SCI) rat model

“…Many studies using the rat SCI model appear to overlook the use of postoperative analgesia, considering the lack of reporting of the use of analgesic regimens in many publications describing this model [31,32,33,34,35]. Where analgesic regimen is reported, variable dosages and durations of administration of analgesics are described, such as acetaminophen 65 mg/kg orally, only if the rat shows the sign of self-mutilation [36]; buprenorphine 0.3mg/kg once daily s/c for two postoperative days [37]; 1.5 ml (0.006 mg/ml) buprenorphine twice daily subcutaneously for first 24–48 hours [38]; and buprenorphine 0.01mg/kg b.i.d.…”

Experimental Spinal Cord Injury Models in Rodents: Anatomical Correlations and Assessment of Motor Recovery

“…Scientists are continuously looking for models that resemble the human injuries more closely. For example, two recent studies focused on lumbosacral SCI, a type of injury affecting an estimated one-third of patients [24,25]. A model combining SCI and traumatic brain injury was recently introduced, because a proportion of SCI patients additionally suffer from head injuries, for example, due to traffic or diving accidents [26].…”