title: Mild TBI Results in a Long-Term Decrease in Circulating Phospholipids in a Mouse Model of Injury.
abstract: Neurophysiological and neurological dysfunction is usually experienced for a short period of time in patients with mild traumatic brain injury (mTBI). However, around 15 % of patients exhibit symptoms months after TBI. Phospholipid (PL) changes have been observed in plasma from mTBI patients at chronic stages, suggesting a role in TBI pathology. We examined long-term plasma phospholipid profiles in a mouse model of mTBI to determine their translational value in reproducing PL changes observed in mTBI patients. Plasma samples were collected at an acute timepoint (24 h post-injury) and at several chronic stages (3, 6, 12 and 24 months post-injury) from injured mice and sham controls. Phospholipids were identified and quantified using liquid chromatography/mass spectrometry analysis. In accordance with human data, we observed significantly lower levels of several major PL classes in mTBI mice compared to controls at chronic timepoints. Saturated, monounsaturated and polyunsaturated fatty acids (PUFAs) were differently regulated over time. As PUFA levels were decreased at 3 months, we measured levels of malondialdehyde to assess lipid peroxidation, which we found to be elevated at this timepoint. Ether-containing PE species were elevated at 24 h post-injury and decreased relative to controls at chronic stages. Arachidonic acid and docosahexaenoic acid-containing species were significantly decreased within all PL classes at the chronic stages. Our findings are similar to changes in PL levels observed in human mTBI subjects. Chronic TBI biomarkers have received little attention, even though disabilities at this stage can be of major importance. Our study provides information on biochemical abnormalities that persist long after the initial injury; these abnormalities may provide useful insight into the continuing pathogenesis and serve as diagnostic biomarkers.
authors.affiliation: The Roskamp Institute, 2040 Whitfield Avenue, Sarasota, FL, 34243, USA. temmerich@roskampinstitute.net.|The Open University, Walton Hall, Milton Keynes, Buckinghamshire, MK7 6AA, UK. temmerich@roskampinstitute.net.|James A. Haley Veteran's Hospital, 13000 Bruce B. Downs Blvd., Tampa, FL, 33612, USA. temmerich@roskampinstitute.net.
authors.forename: Tanja
authors.identifier: 0000-0001-5064-7150
authors.initials: T
authors.lastname: Emmerich
authors.affiliation: The Roskamp Institute, 2040 Whitfield Avenue, Sarasota, FL, 34243, USA.|The Open University, Walton Hall, Milton Keynes, Buckinghamshire, MK7 6AA, UK.|James A. Haley Veteran's Hospital, 13000 Bruce B. Downs Blvd., Tampa, FL, 33612, USA.
authors.forename: Laila
authors.initials: L
authors.lastname: Abdullah
authors.affiliation: The Roskamp Institute, 2040 Whitfield Avenue, Sarasota, FL, 34243, USA.|The Open University, Walton Hall, Milton Keynes, Buckinghamshire, MK7 6AA, UK.
authors.forename: Joseph
authors.initials: J
authors.lastname: Ojo
authors.affiliation: The Roskamp Institute, 2040 Whitfield Avenue, Sarasota, FL, 34243, USA.|The Open University, Walton Hall, Milton Keynes, Buckinghamshire, MK7 6AA, UK.|James A. Haley Veteran's Hospital, 13000 Bruce B. Downs Blvd., Tampa, FL, 33612, USA.
authors.forename: Benoit
authors.initials: B
authors.lastname: Mouzon
authors.affiliation: The Roskamp Institute, 2040 Whitfield Avenue, Sarasota, FL, 34243, USA.
authors.forename: Thinh
authors.initials: T
authors.lastname: Nguyen
authors.affiliation: The Roskamp Institute, 2040 Whitfield Avenue, Sarasota, FL, 34243, USA.|The Open University, Walton Hall, Milton Keynes, Buckinghamshire, MK7 6AA, UK.
authors.forename: Gogce
authors.initials: G
authors.lastname: Crynen
authors.affiliation: The Roskamp Institute, 2040 Whitfield Avenue, Sarasota, FL, 34243, USA.|James A. Haley Veteran's Hospital, 13000 Bruce B. Downs Blvd., Tampa, FL, 33612, USA.
authors.forename: James E
authors.initials: JE
authors.lastname: Evans
authors.affiliation: The Roskamp Institute, 2040 Whitfield Avenue, Sarasota, FL, 34243, USA.|James A. Haley Veteran's Hospital, 13000 Bruce B. Downs Blvd., Tampa, FL, 33612, USA.
authors.forename: Jon
authors.initials: J
authors.lastname: Reed
authors.affiliation: The Roskamp Institute, 2040 Whitfield Avenue, Sarasota, FL, 34243, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Mullan
authors.affiliation: The Roskamp Institute, 2040 Whitfield Avenue, Sarasota, FL, 34243, USA.|The Open University, Walton Hall, Milton Keynes, Buckinghamshire, MK7 6AA, UK.|James A. Haley Veteran's Hospital, 13000 Bruce B. Downs Blvd., Tampa, FL, 33612, USA.
authors.forename: Fiona
authors.initials: F
authors.lastname: Crawford
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000097:blood; D015415:Biomarkers; D001921:Brain / Q000378:metabolism; D001925:Brain Damage, Chronic / Q000097:blood* / Q000209:etiology; D000070642:Brain Injuries, Traumatic / Q000097:blood* / Q000150:complications; D004281:Docosahexaenoic Acids / Q000097:blood; D007249:Inflammation; D015227:Lipid Peroxidation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020675:Peroxisomes / Q000378:metabolism; D010743:Phospholipids / Q000097:blood*; D011897:Random Allocation; D013997:Time Factors
chemical_list: D001095:Arachidonic Acids; D015415:Biomarkers; D010743:Phospholipids; D004281:Docosahexaenoic Acids
keywords: Lipidomics; Mild traumatic brain injury (mTBI); Mouse model; Phospholipids (PL); Plasma biomarkers