Localization of the corticospinal tract within the porcine spinal cord: Implications for experimental modeling of traumatic spinal cord injury

Abstract

Spinal cord injury (SCI) researchers have predominately utilized rodents for SCI modeling and experimentation. Unfortunately, a large number of novel therapies developed in rodent models have failed to demonstrate efficacy in human clinical trials which suggests that improved animal models are an important translational tool. Recently, porcine models of SCI have been identified as a valuable intermediary model for preclinical evaluation of promising therapies to aid clinical translation. However, the localization of the major spinal tracts in pigs has not yet been described. Given that significant differences exist in the location of the corticospinal tract (CST) between rodents and humans, determining its location in pigs will provide important information related to the translational potential of the porcine pre-clinical model of SCI. Thus, the goal of this study is to investigate the localization of the CST within the porcine spinal cord. Mature female domestic pigs (n=4, 60kg) received microinjections of fluorescent dextran tracers (Alexa Fluor, 10,000MW) into the primary motor cortex, using image-guided navigation (StealthStation®), to label the CST. At 5 weeks post-tracer injection animals were euthanized, the entire neuroaxis harvested and processed for histological examination. Serial sections of the brain and spinal cord were prepared and imaged using confocal microscopy to observe the location of the CST in pigs. Results demonstrate that the CST of pigs is located in the lateral white matter, signifying greater similarity to human anatomical structure compared to that of rodents. We conclude that the corticospinal tract in pigs demonstrates anatomical similarity to human, suggesting that the porcine model has importance as a translational intermediary pre-clinical model.