The Effect of 6-chloro-tryptophan on QUIN Accumulation in Spinal Cord Injury

Schimmel/Conrades Science Center Atrium

Spinal cord injuries (SCI) cause motor and sensory deficits, which negatively affect quality of life. These deficits result from the primary deficits caused by the initial injury and secondary deficits due to pathological processes mediated by the inflammatory immune response. Quinolinic acid (QUIN), a neurotoxic molecule that is released by activated immune cells after SCI, contributes to the secondary functional deficits. In previous studies, 4-Chloro-3-hydroxyanthranilate (4Cl-3HAA) was shown to decrease QUIN accumulation after SCI. The goal of this study was to see whether 6-chloro-tryptophan (6-Cl), a precursor to 4Cl-3HAA, was able to produce the same decrease in QUIN and behavioral deficits as 4Cl-3HAA. Hartley guinea pigs underwent a dorsal laminectomy procedure at thoracic level 12. A lateral compression SCI was induced using a custom tool that was used to compress the spinal cord to a thickness of 2mm for 15 seconds. Air righting, contact righting, cutaneus trunci muscle reflex (CTM) receptive field area, proprioceptive placing, toe spread, and incline behavioral tests were conducted 5 hours, 1 day, 2 days, 3 days, 7 days, and 12 days after the injury. The guinea pigs were blindly assigned to either a vehicle or 6-Cl treatment group. Treatments were administered via intraperitoneal injection every 12 hours. The spinal cords were fixed with 5% glutaraldehyde solution. Spinal cords will be sliced to a thickness of 20 microns and immunohistochemistry techniques will be used to quantify the amount of QUIN accumulation at the site of injury at 1, 2, 3, 7, and 12 days post injury.