Rose Marie E, Huerbin Michele B, Melick John, Marion Donald W, Palmer Alan M, Schiding Joanne K, Kochanek Patrick M, Graham Steven H
Department of Neurology, 526 South BST, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Brain Res. 2002 May 10;935(1-2):40-6. doi: 10.1016/s0006-8993(02)02445-9.
Increases in brain interstitial excitatory amino acid (EAA(I)) concentrations after ischemia are ameliorated by use-dependent Na+ channel antagonists and by supplementing interstitial glucose, but the regulation of EAA(I) after traumatic brain injury (TBI) is unknown. We studied the regulation of EAA(I) after TBI using the controlled cortical impact model in rats. To monitor changes in EAA(I), microdialysis probes were placed in the cortex adjacent to the contusion and in the ipsilateral hippocampus. Significant increases in dialysate EAA(I) after TBI were found compared to levels measured in sham controls. Treatment with the use-dependent Na+ channel antagonist 619C89 (30 mg/kg i.v.) did not significantly decrease dialysate glutamate compared to vehicle controls in hippocampus (10.4+/-2.4 vs. 11.9+/-1.6 microM), but there was significant decrease in dialysate glutamate in cortex after 619C89 treatment (19.3+/-3 vs. 12.6+/-1.1 microM P<0.05). Addition of 30 mM glucose to the dialysate, a treatment that decreases EAA(I) after ischemia, had no significant effect upon dialysate glutamate after TBI in cortex (20.0+/-4.9 vs. 11.7+/-3.4 microM) or in hippocampus (10.9+/-2.0 vs. 8.9+/-2.4 microM). These results suggest that neither increased release of EAAs due to Na+ channel-mediated depolarization nor failure of glutamate reuptake due to glucose deprivation can explain the majority of the increase in EAA(I) following TBI.
缺血后脑海马间质兴奋性氨基酸（EAA(I)）浓度的升高可通过使用依赖性钠离子通道拮抗剂及补充间质葡萄糖得到改善，但创伤性脑损伤（TBI）后EAA(I)的调节机制尚不清楚。我们使用大鼠控制皮质撞击模型研究了TBI后EAA(I)的调节机制。为监测EAA(I)的变化，将微透析探针置于挫伤灶附近的皮质及同侧海马中。与假手术对照组相比，TBI后透析液中EAA(I)显著升高。与海马中给予赋形剂对照相比，使用依赖性钠离子通道拮抗剂619C89（30mg/kg静脉注射）治疗并未显著降低透析液中谷氨酸水平（分别为10.4±2.4与11.9±1.6μM），但619C89治疗后皮质透析液中谷氨酸水平显著降低（分别为19.3±3与12.6±1.1μM，P<0.05）。在透析液中添加30mM葡萄糖（一种可降低缺血后EAA(I)的处理方法），对TBI后皮质（分别为20.0±4.9与11.7±3.4μM）或海马（分别为10.9±2.0与8.9±2.4μM）透析液中谷氨酸水平无显著影响。这些结果表明，钠离子通道介导的去极化导致的兴奋性氨基酸释放增加或葡萄糖剥夺导致的谷氨酸再摄取失败均不能解释TBI后EAA(I)升高的主要原因。
