Contrasting Biomechanics and Neuropathology of Spinal Cord Injury in Neonatal and Adult Rats following Vertebral Dislocation

Abstract

Clinically, spinal cord injuries (SCI) in infants are different from SCIs in adults. SCI is rarer in infants, and the most common types of associated spinal column injury are different for adults and infants. Initially, infants tend to have higher injury severities and mortality; however, young survivors of SCI typically have greater and more rapid functional recovery. The objective of this study was to contrast the biomechanics and neuropathology of SCI in adult and neonatal rats to investigate these differences. Thoracolumbar vertebrae of anaesthetized rats were dislocated laterally (T12 held stationary and L1 displaced laterally, with T13 between these levels) by 10 mm at 250 mm/sec in adults and by 4 mm at 100 mm/sec in neonates (13-15 days), and rats were euthanized 6 h later. Spinal cord sections were stained to detect hemorrhage (with hematoxylin and eosin [H&E]), axonal injury (with beta-amyloid precursor protein [betaAPP]), and neuronal nuclei (with NeuN). Maximum load was significantly higher in adults (25.7 +/- 2.4N) than neonates (11.0 +/- 2.4N; p < 0.001). Adult and neonatal hemorrhage volumes were not significantly different for either the raw or normalized data sets (p = 0.064 for normalized dataset). Un-normalized axonal injury densities were similar for adults and neonates, but normalized axonal injury density was significantly higher in neonates (p < 0.001). Reduction of NeuN immunoreactivity was significantly lower in neonates, for both un-normalized (p < 0.004) and normalized (p < 0.001) data sets. The findings of this study may explain the different common types of spinal column injury associated with SCI, and the greater initial severity of SCI in infants.

The mechanical properties of neonatal rat spinal cord in vitro, and comparisons with adult

“…The constitutive model and data presented here may also be useful for computer models of paediatric spinal cord, to allow use of age-appropriate mechanical property information. Experimental models of paediatric SCI, have attempted to match adult SCI model severities by matching spinal cord strain and strain rate, or the speed and magnitude of the experimental injury (Brown et al, 2005;Leung and Wrathall, 2006;Clarke and Bilston, 2008). However, our results suggest that matching the spinal cord strain would likely produce a lower stress in the neonatal spinal cord.…”

“…However, for some experimental models of SCI (for a review of SCI models see Kwon et al, 2002) the comparison between adult and neonatal animals poses the problem of delivering equivalent mechanical injury severities in animals of different sizes. Previous studies using contusion and dislocation models in neonatal ($14 days) and adult rats have attempted to match spinal cord strain and strain rate, or the speed and magnitude of the experimental injury, based on anatomical scaling factors (Brown et al, 2005;Leung and Wrathall, 2006;Clarke and Bilston, 2008). However it is not known whether the mechanical properties of the adult and neonatal spinal cord are comparable, and therefore it is not clear whether anatomical scaling alone produces comparable mechanical loads in adult and neonatal animals.…”

Severity of Spinal Cord Injury in Adult and Infant Rats after Vertebral Dislocation Depends upon Displacement but not Speed

“…The injury conditions for the infant cohort were scaled by a factor of 2.5 based on the measured nerve root separation at T12-T13 (a nominal rostrocaudal geometrical measure) of adult and infant spinal cords, with the purpose of applying equivalent strain and strain rate to adult and infant cords during injury. 8 Biomechanical data were collected from the displacement sensor and load cell connected to the moving beam of the injury device.…”

“…1 Two clinically relevant vertebral dislocation models have been developed, 6,7 and one has been modified for investigating pediatric SCI. 8 Contusion models for experimental SCI are valuable, but vertebral dislocation models offer a unique additional opportunity to study cord injury under loading conditions that more closely mimic the most common mechanisms of SCI in humans.…”

“…9 This pattern of injury, in which SCI is more severe in children than in adults, has also been confirmed experimentally under controlled conditions using a rodent model of vertebral dislocation. 8 Despite this, children tend to have higher rates of neurological improvement, 10 and this has also been demonstrated experimentally in rats by testing locomotor function following spinal cord contusion injury, 11 and transection injury. 12 The severity of SCI is also thought to depend upon the speed and displacement of spinal motion during injury.…”