The impact of aging on locomotor recovery in preclinical models of traumatic spinal cord injury: a systematic review

Introduction Aging is known to influence recovery following spinal cord injury (SCI) however its specific impact on locomotor outcomes remains underexplored. Understanding these age-related differences is critical for developing targeted rehabilitation strategies and improving the translational relevance of SCI research. This systematic review aimed to evaluate the effect of aging on locomotor recovery in animal models of traumatic SCI. Methods A systematic search of MEDLINE and Embase was conducted to identify studies assessing the impact of aging on post-SCI locomotor outcomes. Inclusion criteria encompassed preclinical studies comparing locomotor recovery between young and aged animals following SCI. Extracted data included sample characteristics, SCI model, locomotor outcome measures, timing of evaluation, and key findings. Risk of bias was assessed using the SYRCLE checklist. Results Of 3,118 unique records screened, nine studies met inclusion criteria. Included animals were grouped into young (mean 2.5 months), intermediate (mean 11.4 months), and aged (mean 21.5 months) categories, with individual ages ranging from 4 weeks to 28 months. Six studies used rats and three studies used mice. In total, more than 340 animals were studied. SCI models included cord contusion (6/9, 66.7%), hemisection (2/9, 22.2%), and clip compression (1/9, 11.1%). Seven (7/9, 77.8%) studies employed the Basso, Beattie, Bresnahan (BBB) locomotor score as the primary outcome measure. Older animals demonstrated significantly lower BBB scores post-injury compared to younger counterparts in 100% (7/7) of studies using this outcome. Other measures of locomotor outcomes included the Basso Mouse Scale, CatWalk, and Digigait. Notably, one study reported that pre-injury and post-injury exercise improved locomotor recovery in aged rats to levels comparable with young rats. Conclusion Aging is associated with poorer locomotor recovery following traumatic SCI in preclinical models. These findings underscore the importance of age as a biological variable in SCI research and suggest that rehabilitative interventions, such as exercise, may have potential to mitigate age-related deficits. Future studies should seek to define the mechanistic pathways underlying impaired recovery with age and evaluate targeted therapies that enhance neuroplasticity and functional recovery. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/view/CRD42022230021 .