Department of Anesthesiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.
Anesth Analg. 2011 Mar;112(3):666-73. doi: 10.1213/ANE.0b013e318207c51f. Epub 2011 Jan 13.
Glutamate and glutamate transporters (GTs) (including glutamate/aspartate transporter, glutamate transporter-1, and excitatory amino acid carrier 1) have important roles in the pathogenesis of ischemic neurological injury. The changes in glutamate, GTs, and neuronal injury after subarachnoid hemorrhage (SAH) have not been widely investigated. In this study, we examined the changes in extracellular glutamate concentration, GTs, wall thickness of basilar arteries (BAs), and neuronal degeneration in experimental SAH rats.
An intrathecal microdialysis probe was inserted into male Sprague Dawley rats. SAH was induced using a double-hemorrhage model. To measure glutamate concentrations, extracellular dialysates were collected for 30 minutes before, and daily for 7 days after SAH. Changes in neurological scores, body weight, and BA wall thickness were measured. The neuron degeneration in the hippocampus and the changes of GTs in the cerebral cortex and hippocampus were measured.
Glutamate concentrations were significantly higher in SAH rats from day (D)1 to D7 after SAH compared with the sham rats, especially at D1. A significant body weight reduction and neurological defects were observed at D3 after SAH. The walls of BAs in SAH rats were significantly thicker compared with those of sham rats; the maximum change was observed at D7. Hippocampal neuronal degeneration was observed after SAH and the highest severity was at D7. The expression of GTs was downregulated after SAH and persisted for 7 days.
SAH induced in the double-hemorrhage rat model may produce an excessive and prolonged increase of extracellular glutamate concentrations and downregulation of GTs, which are accompanied by BA wall thickness, and hippocampal neuronal degeneration.
谷氨酸和谷氨酸转运体（GTs）（包括谷氨酸/天冬氨酸转运体、谷氨酸转运体-1 和兴奋性氨基酸载体 1）在缺血性神经损伤的发病机制中具有重要作用。蛛网膜下腔出血（SAH）后谷氨酸、GTs 和神经元损伤的变化尚未得到广泛研究。在这项研究中，我们研究了实验性 SAH 大鼠细胞外谷氨酸浓度、GTs、基底动脉（BA）壁厚度和神经元变性的变化。
雄性 Sprague Dawley 大鼠插入鞘内微透析探针。采用双出血模型诱导 SAH。为了测量谷氨酸浓度，在 SAH 前 30 分钟收集细胞外透析液，并在 SAH 后每天收集 7 天。测量神经评分、体重和 BA 壁厚度的变化。测量海马神经元变性和大脑皮质和海马 GTs 的变化。
与假手术大鼠相比，SAH 大鼠从 SAH 后第 1 天（D1）到第 7 天（D7），谷氨酸浓度明显升高，尤其是在 D1。SAH 后第 3 天观察到明显的体重减轻和神经缺陷。SAH 大鼠的 BA 壁明显比假手术大鼠厚；最大变化发生在 D7。SAH 后观察到海马神经元变性，最严重的程度发生在 D7。SAH 后 GTs 的表达下调，并持续 7 天。
在双出血大鼠模型中诱导的 SAH 可能导致细胞外谷氨酸浓度的过度和持续增加以及 GTs 的下调，同时伴有 BA 壁厚度和海马神经元变性。
