Evolution of Lipid Metabolism in the Injured Mouse Spinal Cord.

Abstract

Following spinal cord injury (SCI), there is a short-lived recovery phase that ultimately plateaus. Understanding changes within the spinal cord over time may facilitate targeted approaches to prevent and/or reverse this plateau and allow for continued recovery. Untargeted metabolomics revealed distinct metabolic profiles within the injured cord during recovery (7 days postinjury [DPI]) and plateau (21 DPI) periods in a mouse model of severe contusion SCI. Alterations in lipid metabolites, particularly those involved in phospholipid (PL) metabolism, largely contributed to overall differences. PLs are hydrolyzed by phospholipases A2 (PLA2s), yielding lysophospholipids (LPLs) and fatty acids (FAs). PL metabolites decreased between 7 and 21 DPI, whereas LPLs increased at 21 DPI, suggesting amplified PL metabolism during the plateau phase. Expression of various PLA2s also differed between the two time points, further supporting dysregulation of PL metabolism during the two phases of injury. FAs, which can promote inflammation, mitochondrial dysfunction, and neuronal damage, were increased regardless of time point. Carnitine can bind with FAs to form acylcarnitines, lessening FA-induced toxicity. In contrast to FAs, carnitine and acylcarnitines were increased at 7 DPI, but decreased at 21 DPI, suggesting a loss of carnitine-mediated mitigation of FA toxicity at the later time point, which may contribute to the cessation of recovery post-SCI. Alterations in oxidative phosphorylation and tricarboxylic acid cycle metabolites were also observed, indicating persistent although dissimilar disruptions in mitochondrial function. These data aid in increasing our understanding of lipid metabolism following SCI and have the potential to lead to new biomarkers and/or therapeutic strategies.