title: Intraparenchymal microdialysis after acute spinal cord injury reveals differential metabolic responses to contusive versus compressive mechanisms of injury.
abstract: In animal models, spinal cord injury (SCI) is typically imparted by contusion alone (e.g., weight drop) or by compression alone (e.g., clip compression). In humans, however, the cord is typically injured by a combination of violent contusion followed by varying degrees of ongoing mechanical compression. Understanding how the combination of contusion and compression influences the early pathophysiology of SCI is important for the pre-clinical development of neuroprotective therapies that are applicable to the human condition. Disturbances in the metabolism of energy-related substrates such as lactate, pyruvate, and glucose are important aspects of secondary damage. In this study, we used a porcine model of traumatic SCI to determine the extent to which these metabolites were influenced by contusion followed by sustained compression, using the microdialysis technique. Following contusion injury, lactate and pyruvate levels near the epicenter both increased, while glucose remained quite stable. When the contusion injury was followed by sustained compression, we observed a transient rise in lactate, while pyruvate and glucose levels dropped rapidly, which may reflect decreased regional spinal cord blood flow. Furthermore, contusion with sustained compression produced a prolonged and dramatic increase in the lactate-pyruvate (L/P) ratio as a marker of tissue hypoxia, whereas after contusion injury alone, a transient and less significant elevation of the L/P ratio was observed. In this study, we demonstrate that disturbances in energy metabolism within the injured spinal cord vary greatly depending upon the biomechanical nature of the injury. Such differences are likely to be relevant to the applicability of novel therapies targeting specific aspects of the early secondary injury cascade after acute human SCI.
authors.affiliation: International Collaboration on Repair Discoveries, University of British Columbia, Vancouver, Canada.
authors.forename: Elena B
authors.initials: EB
authors.lastname: Okon
authors.forename: Femke
authors.initials: F
authors.lastname: Streijger
authors.forename: Jae H T
authors.initials: JH
authors.lastname: Lee
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Anderson
authors.forename: Amy K
authors.initials: AK
authors.lastname: Russell
authors.forename: Brian K
authors.initials: BK
authors.lastname: Kwon
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology; D005260:Female; D005947:Glucose / Q000134:cerebrospinal fluid; D006339:Heart Rate / Q000502:physiology; D007511:Ischemia / Q000134:cerebrospinal fluid / Q000378:metabolism; D019344:Lactic Acid / Q000134:cerebrospinal fluid; D017551:Microdialysis / Q000295:instrumentation / Q000379:methods*; D019289:Pyruvic Acid / Q000134:cerebrospinal fluid; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D013117:Spinal Cord Compression / Q000378:metabolism* / Q000473:pathology*; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000473:pathology*; D013552:Swine; D013556:Swine, Miniature
chemical_list: D019344:Lactic Acid; D019289:Pyruvic Acid; D005947:Glucose