title: Glial cell-mediated deterioration and repair of the nervous system after traumatic brain injury in a rat model as assessed by positron emission tomography.
abstract: Traumatic brain injury (TBI) is one of the most acute degenerative pathologies in the central nervous system, and in vivo indices enabling an assessment of TBI on a mechanistic basis have yet to be established. The aim of this work was to pursue neuroinflammatory changes and their link to functional disruptions of traumatically-damaged neurons in a rat model of TBI by longitudinal positron emission tomographic (PET) assays. TBI was induced in the unilateral frontal cortex of craniotomied rats according to a lateral fluid percussion brain injury protocol. The use of [(18)F]fluoroethyl-DAA1106 as a PET tracer for translocator protein (TSPO) permitted demonstration of the inflammatory response to the injury, peaking at 1 week after impact. This alteration was parallel to metabolic deficits assessed by PET with [(18)F]fluorodeoxyglucose, but the difference in TSPO levels between impacted and non-impacted frontal cortices was more than threefold of the interlateral metabolic difference, indicating superiority of TSPO imaging for sensitive detection of post-traumatic pathologies. Comparative PET, autoradiographic. and immunohistochemical investigations illustrated the primary contribution of hypertrophic microglia and macrophages to acute TSPO signals in the vicinity of the impact. Astrocytes also formed a TSPO-positive glial scar encompassing necrotic inflammation, and were clustered with PET-detectable TSPO signals in the bilateral external and internal capsules at late stages, putatively reacting with diffuse axonal injury. These observations support the applicability of TSPO-PET as an imaging-based preclinical and clinical biomarker assay in TBI, and indicate its potential capability to clarify aggressive and protective roles of glial responses to injury when combined with emerging anti-inflammatory and immunomodulatory treatments.
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Iwae
authors.initials: I
authors.lastname: Yu
authors.forename: Motoki
authors.initials: M
authors.lastname: Inaji
authors.forename: Jun
authors.initials: J
authors.lastname: Maeda
authors.forename: Takashi
authors.initials: T
authors.lastname: Okauchi
authors.forename: Tadashi
authors.initials: T
authors.lastname: Nariai
authors.forename: Kikuo
authors.initials: K
authors.lastname: Ohno
authors.forename: Makoto
authors.initials: M
authors.lastname: Higuchi
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Suhara
mesh_terms: D000818:Animals; D001345:Autoradiography; D020201:Brain Hemorrhage, Traumatic / Q000000981:diagnostic imaging* / Q000473:pathology; D019788:Fluorodeoxyglucose F18; D005911:Gliosis / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D000226:Mitochondrial ADP, ATP Translocases / Q000378:metabolism; D009416:Nerve Regeneration / Q000502:physiology*; D009457:Neuroglia / Q000502:physiology*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D051381:Rats; D017208:Rats, Wistar
chemical_list: D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D000226:Mitochondrial ADP, ATP Translocases