Dorsolateral Funiculus Lesioning of the Mouse Cervical Spinal Cord at C4 but Not at C6 Results in Sustained Forelimb Motor Deficits

Although upper extremity functional recovery is a high priority for spinal cord injured patients with cervical injuries, few injury models have been developed in mice with sustained deficits in forelimb motor function. Here, we characterize a dorsolateral funiculus (DLF) crush model in mice, which ablates the rubrospinal tract (RST) unilaterally and thus allows correlation of motor recovery to axonal regeneration in the assessment of molecular regeneration targets. We conducted unilateral DLF crush injuries at cervical levels C4 and C6 and assessed motor recovery in a battery of tests: the rearing test of forelimb asymmetry, the grooming test, staircase pellet reaching, a horizontal ladder task, and CatWalk gait analysis. All tasks revealed lesion effects on forepaw function when DLF crush was instigated at level C4, but deficits were generally only transient in mice with DLF crush performed at level C6. Anterograde tracing of the RST with biotinylated dextran amine revealed the tract's complete ablation. The characterization of a C4 DLF model in mice provides an important tool for assessing molecular regeneration targets to promote functional recovery after spinal cord injury.