Neurosurgical Center Amsterdam, VU University Medical Center, De Boelelaan 1117, NL-1081 HV Amsterdam, The Netherlands.
J Neuroinflammation. 2011 Jun 14;8:67. doi: 10.1186/1742-2094-8-67.
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)-[(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.
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.
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.
本研究的目的是调查创伤性脑损伤（TBI）后小胶质细胞的激活情况，并将这些发现与谷氨酸释放联系起来。
使用皮质撞击法或假手术，在 TBI 前 24 小时（基线）和 1 天及 10 天后，对大鼠进行连续动态 [(11)C]PK11195 PET 扫描。使用脑微透析测量细胞外液（ECF）谷氨酸浓度。对大脑进行组织病理学和（免疫）组织化学处理。
与基线值和假手术对照组相比，TBI 大鼠在 TBI 后 10 天的 [(11)C]PK11195 结合明显增加（p < 0.05）。与假手术相比，TBI 后即刻 ECF 谷氨酸值升高（27.6 ± 14.0 μmol·L(-1)）（6.4 ± 3.6 μmol·L(-1)）。TBI 与假手术之间在 ED-1、OX-6、GFAP、Perl's 和 Fluoro-Jade B 方面存在显著差异。
TBI 后 10 天大脑对 [(11)C]PK11195 的摄取增加表明小胶质细胞的持续激活。这种激活伴随着 ECF 谷氨酸水平的急性创伤后显著增加。
