Metabolite Profiles Correlate Closely with Neurobehavioral Function in Experimental Spinal Cord Injury in Rats 英文参考文献.docVIP

MetaboliteProfilesCorrelateCloselywith NeurobehavioralFunctioninExperimentalSpinalCord InjuryinRats YusukeFujieda1,2*,ShinyaUeno2,RyokoOgino2,MarikoKuroda2,ThomasJ.Jo¨nsson3,LiningGuo3, TakeshiBamba1,EiichiroFukusaki1* 1DepartmentofBiotechnology,GraduateSchoolofEngineering,OsakaUniversity,Suita,Japan,2AsubioPharmaCo.,Limited,Kobe,Japan,3MetabolonInc.,Durham, NorthCarolina,UnitedStatesofAmerica Abstract 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 inflammatoryresponseconsistingofelevatedlevelsofprostaglandinE2andpalmitoylethanolamideaswellaspro-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 v-3 fatty acids docosapentaenoate and docosahexaenoate correlated greatly with the established Basso, Beattie and Bresnahan locomotivescore(BBBscore).OurfindingssuggestthepossibilityofabiochemicalbasisforBBBscoreandillustratethat metabolitesmaycorrelatewithneurobehavior.InparticulartheNAAlevelinthespinalcordmightprovideameaningful biomarkerthatcouldhelptodeterminethedegreeofinjuryseverityandprognosticateneurologicrecovery. Citation:FujiedaY,UenoS,OginoR,KurodaM,Jo¨nssonTJ,etal.(2012)MetaboliteProfilesCorrelateCloselywithNeurobehavioralFunctioninExperimental SpinalCordInjury