Functional and Histological Gender Comparison of Age-Matched Rats after Moderate Thoracic Contusive Spinal Cord Injury

Abstract

Spinal cord injury (SCI) afflicts hundreds of thousands of Americans, and most SCI (*80%) occurs in males. In experimental animal models, however, many studies used females. Funding agencies like the National Institutes of Health recommend that new proposed studies should include both genders due to variations in gender response to injuries, diseases, and treatments. However, cost and considerations for some animal models, such as SCI, affect investigators in adapting to this recommendation. Research has increased comparing gender effects in various disease and injury models, including SCI. However, most studies use weight-matched animals, which poses issues in comparing results and outcomes. The present study compared histologic and functional outcomes between age-matched male and female Sprague-Dawley rats in a moderate thoracic contusion SCI model. Cresyl violet and eosin staining showed no significant differences in lesion volume between genders after 9 weeks post-SCI (p > 0.05). Luxol fast blue-stained spared myelin was similar between genders, although slightly greater (*6%) in spared myelin, compared with cord volume (p = 0.044). Glial reactivity and macrophage labeling in the lesion area was comparable between genders, as well. Basso, Beattie, Bresnahan (BBB) functional scores were not significantly different between genders, and Hargreaves thermal hyperalgesia and Gridwalk sensorimotor analyses also were similar between genders, compared with uninjured gender controls. Analysis of covariance showed weight did not influence functional recovery as assessed through BBB (p = 0.65) or Gridwalk assessment (p = 0.63) in this study. In conclusion, our findings suggest age-matched male and female rats recover similarly in a common clinically relevant SCI model.

Considerations for Studying Sex as a Biological Variable in Spinal Cord Injury

“…The extent to which sex influences outcomes following SCI remains controversial based on existing clinical and pre-clinical data. Several rodent studies have confirmed a female-biased protection on locomotor outcomes after SCI ( 14 – 17 ), while others have found no differences ( 18 , 19 ). Most prior work supporting sex-dependent effects after SCI have limited evaluations to locomotor outcomes and white matter sparing, which found marginal improvements favoring females.…”

Acute inflammatory profiles differ with sex and age after spinal cord injury

“…There is increasing evidence that the pathophysiology and recovery after SCI may be sex-dependent [13,14,[18][19][20][21][22][23]. This is especially true for neuropathic pain where sexdependent outcomes have been observed in both humans and rodents [24][25][26].…”

The Involvement of CaV1.3 Channels in Prolonged Root Reflexes and Its Potential as a Therapeutic Target in Spinal Cord Injury

“…Only female nice were chosen because it is easier to express the bladders of female SCI mice and they have lower risk of complication ( Lilley et al, 2020 ). In addition, the study with only female mice are unlikely to cause experimental bias because the pathophysiology in male and female SCI animals appears to be similar ( Walker et al, 2019 ). The feasibility of the mouse model for this study is based on the facts that MNs in the mouse spinal cord are known to contain PICs ( Meehan et al, 2010 ), and spasms and enhanced spinal cord reflex have been well demonstrated in the SCI models with injury at T9-10 ( Skinner et al, 1996 ; Corleto et al, 2015 ; Tysseling et al, 2017 ; Mekhael et al, 2019 ).…”