Effects of 6-Chloro-Tryptophan on Acute Spinal Cord Injury in Guinea Pigs

Students: Brian Jordan, Brooklyn McCue (Columbus State Community College), Austin Minnick, and Cemaliye Semmedi
Mentor: Jennifer Yates (Department of Psychology, Neuroscience Program)

Spinal cord injuries affect thousands of people every year and available treatment therapies are insufficient. Much of the damage from spinal cord injury occurs after the initial impact in what is called the secondary injury. As an alternative to current treatments, our experiment focuses on the effects of a drug called 6-chloro-tryptophan in treating secondary injury. We found that certain doses of the drug appeared to improve recovery of injured animals over the course of one week.

Inflammation contributes to the secondary behavioral deficits seen in neurotraumatic injuries such as spinal cord injury (SCI). The current approved treatment for SCI primarily exists as an antioxidant that fails to reduce inflammation. Inflammation in acute SCI is associated with the production of the neurotoxin, quinolinic acid (QUIN). QUIN is produced by activated macrophages at the injury site and its accumulation is correlated with injury severity. Previous studies have shown that manipulating the tryptophan-kynurenine pathway, which leads to the production of QUIN, can attenuate QUIN accumulation and reduce secondary behavioral deficits after SCI. One way to manipulate this pathway is by administering 6-chloro-tryptophan. In the present study, the effects of 6-chloro-tryptophan on secondary behavioral deficits and QUIN accumulation were investigated in a guinea pig model of SCI. Adult female Hartley guinea pigs were injured by lateral compression of the spinal cord at the 12th thoracic segment (T12). 6-chloro-tryptophan was administered in doses of 1 mg, 5 mg, 7.5 mg, and 10 mg over a time period of either 3 or 7 days, beginning at 5 hours post injury. The severity of the behavioral deficits and the recovery rate of the subjects were quantified using several sensory and motor function tests, including Cutaneus Trunci muscle reflex, toe-spread, proprioceptive placing etc. Doses between 5-10 mg showed trending improvement in recovery rate. Supplementary histological analysis will be required to quantify QUIN accumulation at the injury site. In order to consider the drug viable, further experimentation will be conducted.