TY - JOUR
T1 - Increased cerebral (R)-[11C]PK11195 uptake and glutamate release in a rat model of traumatic brain injury
T2 - A longitudinal pilot study
AU - Folkersma, Hedy
AU - Foster Dingley, Jessica C.
AU - van Berckel, Bart N.M.
AU - Rozemuller, Annemieke
AU - Boellaard, Ronald
AU - Huisman, Marc C.
AU - Lammertsma, Adriaan A.
AU - Vandertop, W. Peter
AU - Molthoff, Carla F.M.
PY - 2011/6/14
Y1 - 2011/6/14
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=79958277386&partnerID=8YFLogxK
U2 - 10.1186/1742-2094-8-67
DO - 10.1186/1742-2094-8-67
M3 - Article
C2 - 21672189
AN - SCOPUS:79958277386
SN - 1742-2094
VL - 8
JO - Journal of Neuroinflammation
JF - Journal of Neuroinflammation
M1 - 67
ER -