title: Increased cerebral (R)-[(11)C]PK11195 uptake and glutamate release in a rat model of traumatic brain injury: a longitudinal pilot study.
abstract: BACKGROUND
  The aim of the present study was to investigate microglia activation over time following traumatic brain injury (TBI) and to relate these findings to glutamate release.
  
  
  METHODS
  Sequential dynamic (R)-[(11)C]PK11195 PET scans were performed in rats 24 hours before (baseline), and one and ten days after TBI using controlled cortical impact, or a sham procedure. Extracellular fluid (ECF) glutamate concentrations were measured using cerebral microdialysis. Brains were processed for histopathology and (immuno)-histochemistry.
  
  
  RESULTS
  Ten days after TBI, (R)-[(11)C]PK11195 binding was significantly increased in TBI rats compared with both baseline values and sham controls (p < 0.05). ECF glutamate values were increased immediately after TBI (27.6 ± 14.0 μmol·L(-1)) as compared with the sham procedure (6.4 ± 3.6 μmol·L(-1)). Significant differences were found between TBI and sham for ED-1, OX-6, GFAP, Perl's, and Fluoro-Jade B.
  
  
  CONCLUSIONS
  Increased cerebral uptake of (R)-[(11)C]PK11195 ten days after TBI points to prolonged and ongoing activation of microglia. This activation followed a significant acute posttraumatic increase in ECF glutamate levels.
authors.affiliation: Neurosurgical Center Amsterdam, VU University Medical Center, De Boelelaan 1117, NL-1081 HV Amsterdam, The Netherlands. h.folkersma@amc.nl
authors.forename: Hedy
authors.initials: H
authors.lastname: Folkersma
authors.forename: Jessica C
authors.initials: JC
authors.lastname: Foster Dingley
authors.forename: Bart N M
authors.initials: BN
authors.lastname: van Berckel
authors.forename: Annemieke
authors.initials: A
authors.lastname: Rozemuller
authors.forename: Ronald
authors.initials: R
authors.lastname: Boellaard
authors.forename: Marc C
authors.initials: MC
authors.lastname: Huisman
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Lammertsma
authors.forename: W Peter
authors.initials: WP
authors.lastname: Vandertop
authors.forename: Carla F M
authors.initials: CF
authors.lastname: Molthoff
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D001930:Brain Injuries / Q000000981:diagnostic imaging* / Q000378:metabolism*; D002250:Carbon Radioisotopes / Q000737:chemistry / Q000378:metabolism*; D005456:Fluorescent Dyes / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D007546:Isoquinolines / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D010865:Pilot Projects; D049268:Positron-Emission Tomography / Q000379:methods; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000970:Antineoplastic Agents; D002250:Carbon Radioisotopes; D005456:Fluorescent Dyes; D007546:Isoquinolines; D018698:Glutamic Acid; C037850:PK 11195