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

Increased cerebral (R)-[(11)C]PK11195 uptake and glutamate release in a rat model of traumatic brain injury: a longitudinal pilot study.
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DOI:
10.1186/1742-2094-8-67
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发表时间:
2011-06-14
影响因子:
9.3
通讯作者:
Molthoff CF
Molthoff CF
中科院分区:
医学1区
文献类型:
--
作者:
Folkersma H;Foster Dingley JC;van Berckel BN;Rozemuller A;Boellaard R;Huisman MC;Lammertsma AA;Vandertop WP;Molthoff CF

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本研究的目的是调查小胶质细胞激活随着时间的推移创伤性脑损伤(TBI),并将这些发现与谷氨酸释放。在TBI前24小时(基线)和TBI后1天和10天,使用受控皮质撞击或假手术对大鼠进行连续动态(R)-[11 C] PK 11195 PET扫描。细胞外液(ECF)谷氨酸浓度测定脑微透析。对脑进行组织病理学和(免疫)组织化学处理。TBI后10天,与基线值和假手术对照相比,TBI大鼠中的(R)-[11 C] PK 11195结合显著增加(p < 0.05)。脑损伤后即刻ECF谷氨酸值(27.6 ± 14.0 μmol·L-1)较假手术组(6.4 ± 3.6 μmol·L-1)明显升高。在TBI和假手术之间发现艾德-1、OX-6、GFAP、Perl's和Fluoro-Jade B的显著差异。脑外伤后10天(R)-[11 C] PK 11195的脑摄取增加表明小胶质细胞的长期和持续活化。这种激活后,ECF谷氨酸水平的显着急性创伤后增加。
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. 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. 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. 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.
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