Increased cerebral (R)-[(11)C]PK11195 uptake and glutamate release in a rat model of traumatic brain injury: a longitudinal pilot study

J Neuroinflammation. 2011 Jun 14;8:67. doi: 10.1186/1742-2094-8-67.

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.

Procedures: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / metabolism
  • Brain / metabolism*
  • Brain / pathology
  • Brain Injuries / diagnostic imaging*
  • Brain Injuries / metabolism*
  • Carbon Radioisotopes / chemistry
  • Carbon Radioisotopes / metabolism*
  • Fluorescent Dyes / metabolism
  • Glutamic Acid / metabolism*
  • Isoquinolines / chemistry
  • Isoquinolines / metabolism*
  • Male
  • Microdialysis
  • Pilot Projects
  • Positron-Emission Tomography / methods
  • Rats
  • Rats, Wistar

Substances

  • Antineoplastic Agents
  • Carbon Radioisotopes
  • Fluorescent Dyes
  • Isoquinolines
  • Glutamic Acid
  • PK 11195