title: Spinal Cord Transcriptomic and Metabolomic Analysis after Excitotoxic Injection Injury Model of Syringomyelia.
abstract: Syringomyelia is a condition of the spinal cord in which a syrinx, or fluid-filled cavity, forms from trauma, malformation, or general disorder. Previous work has shown that in noncanalicular syringomyelia irregular flow and pressure conditions enhance the volumetric growth of syrinxes. A better understanding of the underlying molecular pathways associated with syrinx formation will unveil targets for treatments and possibly prevention of syringomyelia in the future. In this study, we performed an established surgical induction of a syrinx using quisqualic acid and kaolin injections in rats to characterize the injury at the molecular level by RNA sequencing and metabolomics techniques at three and six weeks post-injury. Syrinxes averaging nearly 10 mm in length formed in the rats' spinal cords; however, smaller syrinxes were also detected in saline injected surgical shams, complicating interpretation of results. Our current results indicate a robust immune response coupled with overall decreases in neuronal signal transmission of syrinx containing animals compared with controls. Although transcriptional changes indicated gliosis and loss of neurons, no neuropathic pain was detected by von Frey allodynia testing. Unique transporters were revealed to be highly dysregulated, including significant increases in betaine/glycine transporter (BGT-1), K+/Cl- co-transporter (KCC4), and aquaporin 1 (AQP1), along with the upregulation of small molecule osmolytes taurine and betaine. The identified metabolites are of particular interest because of their involvement in osmotic homeostasis and need to be investigated further for their specific involvement in trauma-induced syrinxes.
authors.affiliation: 1 Department of Chemical and Biomolecular Engineering, University of Akron , Akron, Ohio.
authors.forename: Ashley E
authors.initials: AE
authors.lastname: Mohrman
authors.affiliation: 2 Department of Integrated Biosciences Program, University of Akron , Akron, Ohio.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Farrag
authors.affiliation: 3 Department of Chemistry, University of Akron , Akron, Ohio.
authors.forename: He
authors.initials: H
authors.lastname: Huang
authors.affiliation: 4 Centre for Genomic Regulation, The Barcelona Institute of Science and Technology , Barcelona, Spain .
authors.forename: Stephan
authors.initials: S
authors.lastname: Ossowski
authors.affiliation: 5 Langley Porter Psychiatric Institute, University of California San Francisco , San Francisco, California.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Haft
authors.affiliation: 3 Department of Chemistry, University of Akron , Akron, Ohio.
authors.forename: Leah P
authors.initials: LP
authors.lastname: Shriver
authors.affiliation: 1 Department of Chemical and Biomolecular Engineering, University of Akron , Akron, Ohio.
authors.forename: Nic D
authors.initials: ND
authors.lastname: Leipzig
mesh_terms: D000818:Animals; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D007111:Immunity, Cellular / Q000187:drug effects / Q000502:physiology; D018836:Inflammation Mediators / Q000378:metabolism*; D008297:Male; D055432:Metabolomics / Q000379:methods*; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D013595:Syringomyelia / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D059467:Transcriptome / Q000187:drug effects / Q000502:physiology*
chemical_list: D018690:Excitatory Amino Acid Agonists; D018836:Inflammation Mediators
keywords: metabolomics; molecular transporters; spinal cord injury; syringomyelia; transcriptomics