Metabolite profiles correlate closely with neurobehavioral function in experimental spinal cord injury in rats.
Traumatic spinal cord injury (SCI) results in direct physical damage and the generation of local factors contributing to secondary pathogenesis. Untargeted metabolomic profiling was used to uncover metabolic changes and to identify relationships between metabolites and neurobehavioral functions in the spinal cord after injury in rats. In the early metabolic phase, neuronal signaling, stress, and inflammation-associated metabolites were strongly altered. A dynamic inflammatory response consisting of elevated levels of prostaglandin E2 and palmitoyl ethanolamide as well as pro- and anti-inflammatory polyunsaturated fatty acids was observed. N-acetyl-aspartyl-glutamate (NAAG) and N-acetyl-aspartate (NAA) were significantly decreased possibly reflecting neuronal cell death. A second metabolic phase was also seen, consistent with membrane remodeling and antioxidant defense response. These metabolomic changes were consistent with the pathology and progression of SCI. Several metabolites, including NAA, NAAG, and the ω-3 fatty acids docosapentaenoate and docosahexaenoate correlated greatly with the established Basso, Beattie and Bresnahan locomotive score (BBB score). Our findings suggest the possibility of a biochemical basis for BBB score and illustrate that metabolites may correlate with neurobehavior. In particular the NAA level in the spinal cord might provide a meaningful biomarker that could help to determine the degree of injury severity and prognosticate neurologic recovery.
Department of Biotechnology, Graduate School of Engineering, Osaka University, Suita, Japan.
Yusuke
Y
Fujieda
Shinya
S
Ueno
Ryoko
R
Ogino
Mariko
M
Kuroda
Thomas J
TJ
Jönsson
Lining
L
Guo
Takeshi
T
Bamba
Eiichiro
E
Fukusaki
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D015232:Dinoprostone / Q000378:metabolism; D004151:Dipeptides / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D008124:Locomotion / Q000502:physiology*; D055442:Metabolome / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000503:physiopathology*; D053719:Tandem Mass Spectrometry
D004151:Dipeptides; D005231:Fatty Acids, Unsaturated; C027172:isospaglumic acid; D015232:Dinoprostone