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Preclinical Models of Spinal Cord Injury

A cure for traumatic spinal cord injury (SCI) remains elusive. Numerous promising therapies have failed in human clinical trials thereby underscoring the need for extensive preclinical testing of pharmacotherapies prior to the initiation of human trials. PsychoGenics utilizes the Infinite Horizon SCI model to screen the efficacy of novel therapies for SCI.

Figure 1: Basso-Beattie-Bresnahan (BBB) locomotor scores following graded thoracic spinal cord contusion injury. The BBB is a widely used metric for assessing recovery in the thoracic spinal cord injury model in rats. Scores in the early phase (0-7) characterize progressive recovery of slight to extensive movements of the hip, knee, and ankle joints. The intermediate phase (8-13) captures sweeping movements of the hind limbs which progresses to plantar stepping with increasing degrees of weight-support and forelimb-hindlimb coordination. The late phase (14-21) scores the orientation of paw placements, toe clearance, tail position and trunk stability during locomotion.

Figure 2: Paw placement following SCI. (A) Foot faults during horizontal ladder crossing at 6 weeks following graded thoracic spinal cord contusion. The horizontal ladder has random spacing between rungs which challenge the animals to accurately grasp the ladder rungs with their paws during traversal. Post-traumatic deficits in gross and fine motor dexterity increases the number of foot fault errors where the animal’s paw slips between the ladder rungs. (B) Gait changes following graded SCI.

Figure 3: NeuroCube® Analysis. Paw placement in normal (A) and SCI (B) animals in NeuroCube® give discrimination value of 92%.

Figure 4: Spinal cord histology and SCI lesion volumes. Repre-sentative lesions at 5 weeks following SCI. 200 kdyne impact force produces larger SCI lesions than 100 kdyne (**p<0.01).