Open Access Research

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

Hedy Folkersma1*, Jessica C Foster Dingley2, Bart NM van Berckel2, Annemieke Rozemuller3, Ronald Boellaard2, Marc C Huisman2, Adriaan A Lammertsma2, W Peter Vandertop1 and Carla FM Molthoff2

Author Affiliations

1 Neurosurgical Center Amsterdam, VU University Medical Center, De Boelelaan 1117, NL-1081 HV Amsterdam, the Netherlands

2 Department of Nuclear Medicine & PET Research, VU University Medical Center, De Boelelaan 1117, NL-1081 HV Amsterdam, the Netherlands

3 Department of Pathology, VU University Medical Center, De Boelelaan 1117, NL-1081 HV Amsterdam, the Netherlands

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Journal of Neuroinflammation 2011, 8:67  doi:10.1186/1742-2094-8-67

Published: 14 June 2011

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)-[11C]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)-[11C]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)-[11C]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.