Sensory Deficits in mice with Lateral Spinal Cord Hemisection Mimic the Brown-Sequard Syndrome

Spinal cord injury (SCI) often results in permanent sensory deficits, significantly impairing quality of life. These deficits are poorly addressed due to a lack of valid animal models with translational relevance. Here, we utilized a thoracic level 8 lateral hemisection SCI mouse model (including both male and female mice) and applied a battery of behavioral assays requiring supraspinal transmission of sensory information, while also assessing ascending spinal circuits from the lumbar spinal cord to the brain. By 28 days post-SCI, sensory assessments revealed distinct deficits: reduced innocuous sensation in the ipsilateral hindpaw and enhanced sensation in the contralateral hindpaw. Both hindlimbs exhibited disrupted nocifensive behaviors, with chronic neuropathic dysesthesia observed only in the contralateral hindlimb. We provided anatomical evidence to elucidate the neural substrates responsible for these sensory discrepancies. This SCI mouse model mimics key features of human lateral hemisection conditions (Brown-Séquard Syndrome) and offers a robust platform to explore underlying mechanisms and develop new therapeutic strategies. Significance statement We present and validate a T8 lateral hemisection model that reproduces the hallmark sensory syndromes of Brown-Séquard syndrome (BSS). Systematic behavioral testing—spanning light-touch, nocifensive, and dysesthesia assays—combined with viral tracing of ascending pathways demonstrates that this single, reproducible lesion recreates the asymmetric sensory loss and chronic contralateral dysesthesia typical of BSS. By tightly matching clinical observations to pre-clinical read-outs, the model offers a powerful platform for dissecting the mechanisms of SCI-induced sensory deficits and for evaluating targeted therapies.