Rat Substrains Differ in the Magnitude of Spontaneous Locomotor Recovery and in the Development of Mechanical Hypersensitivity after Experimental Spinal Cord Injury

Abstract

A number of different rodent experimental models of spinal cord injury have been used in an attempt to model the pathophysiology of human spinal cord injury. As a result, interlaboratory comparisons of the outcome measures can be difficult. Further complicating interexperiment comparisons is the fact that the rodent response to different experimental models is strain-dependent. Moreover, the literature is abundant with examples in which the same injury model and strain result in divergent functional outcomes. The objective of this research was to determine whether substrain differences influence functional outcome in experimental spinal cord injury. We induced mild contusion spinal cord injuries in three substrains of Sprague-Dawley rats purchased from three different European breeders (Scanbur, Charles River, and Harlan) and evaluated the impact of injury on spontaneous locomotor function, hypersensitivity to mechanical stimulation, and bladder function. We found that Harlan rats regained significantly more hindlimb function than Charles River and Scanbur rats. We also observed substrain differences in the recovery of the ability to empty the bladder and development of hypersensitivity to mechanical stimulation. The Harlan substrain did not show any signs of hypersensitivity in contrast to the Scanbur and Charles River substrains, which both showed transient reduction in paw withdrawal thresholds. Lastly, we found histological differences possibly explaining the observed behavioral differences. We conclude that in spite of being the same strain, there might be genetic differences that can influence outcome measures in experimental studies of spinal cord injury of Sprague-Dawley rats from different vendors.

Rat models of spinal cord injury: from pathology to potential therapies

“…Notably, rats recover from spinal cord injury in a strain-specific manner (Mills et al, 2001), and even substrain-specific differences in functional outcome and tissue sparing exists (Kjell et al, 2013). The reasons for these differences are not well understood but seem to be genetic.…”

“…Sensory disturbances such as allodynia (a condition in which touch elicits pain) and neurogenic pain (a condition featuring pathological increases in pain) can manifest in patients. Mild spinal cord injuries in rats typically cause a longer period of hypersensitivity to mechanical and thermal stimuli (although some rats display loss of sensory function) (Kjell et al, 2013). Like human patients, rats with severe spinal cord injuries can develop allodynia (Bruce et al, 2002; Hofstetter et al, 2005).…”

Using gait analysis to assess weight bearing in rats with Freund׳s complete adjuvant-induced monoarthritis to improve predictivity: Interfering with the cyclooxygenase and nerve growth factor pathways

“…The most common method to subject rats to spinal contusion injury is by using a dedicated instrument called Impactor. (Abrams et al, 2012, Gruner J.A, 1992, Kjell et al, 2013 The dorsal surface of the spinal cord is exposed by laminectomy of the spinal column (at T9 and the caudal half of T10) and by dropping a 10 g weight from a specified height onto the spinal cord e.g. 12.5 or 25 mm to induce a mild or moderate contusion injury, respectively.…”

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

“…The strain of the animals (and even the substrain produced by different suppliers) also plays an important role. Some animal strains perform better than others in tests which require the acquisition of certain skills [118,120]. For example, in the staircase-skilled forepaw reaching test, Lister-hooded and Long-Evans rats perform much better than Lewis rats and Fischer rats [121,122].…”