• Zachary A Graham, Jacob A Siedlik, Lauren Harlow, Karim Sahbani, William A Bauman, Hesham A Tawfeek, and Christopher P Cardozo.
• National Center for the Medical Consequences of Spinal Cord Injury, James J. Peters VA Medical Center, Bronx, New York.
• J. Neurotrauma. 2019 Sep 15; 36 (18): 2722-2731.

AbstractSpinal cord injury (SCI) results in rapid muscle atrophy and an oxidative-to-glycolytic fiber-type shift. Those with chronic SCI are more at risk for developing insulin resistance and reductions in glucose clearance than able-bodied individuals, but how glucose metabolism is affected after SCI is not well known. An untargeted metabolomics approach was utilized to investigate changes in whole-muscle metabolites at an acute (7-day) and subacute (28-day) time frame after a complete T9 spinal cord transection in 20-week-old female C57BL/6 mice. Two hundred one metabolites were detected in all samples, and 83 had BinBase IDs. A principal components analysis showed the 7-day group as a unique cluster. Further, 36 metabolites were altered after 7- and/or 28-day post-SCI (p values <0.05), with 12 passing further false discovery rate exclusion criteria; of those 12 metabolites, three important glycolytic molecules-glucose and downstream metabolites pyruvic acid and lactic acid-were reduced at 7 days compared to those values in sham and/or 28-day animals. These changes were associated with altered expression of proteins associated with glycolysis, as well as monocarboxylate transporter 4 gene expression. Taken together, our data suggest an acute disruption of skeletal muscle glucose uptake at 7 days post-SCI, which leads to reduced pyruvate and lactate levels. These levels recover by 28 days post-SCI, but a reduction in pyruvate dehydrogenase protein expression at 28 days post-SCI implies disruption in downstream oxidation of glucose.

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