Massieu L, Tapia R
Departamento de Neurociencias, Universidad Nacional Autónoma de México, D.F., México.
Neuroscience. 1994 Apr;59(4):931-8. doi: 10.1016/0306-4522(94)90296-8.
In the present work we have tested the neuroprotective effect of 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX) on the excitotoxic damage induced by the injection of several glutamate receptor agonists into the rat striatum. NBQX was co-injected with each of the agonists studied (1 microliter) in the striatum and damage was assessed by the determination of both glutamate decarboxylase and choline acetyltransferase activities in striatal homogenates, five days after the lesion. Additionally, animals were transcardially perfused with 0.9% saline/4% paraformaldehyde and brain coronal sections were stained with Cresyl Violet for histological analysis. Our results show that NBQX (25 nmol) did not protect against the damage induced by the intrastriatal injection of 200 nmol quinolinic acid monitored by either choline acetyltransferase or glutamate decarboxylase activity. In contrast, the same concentration of NBQX partially protected against 200 nmol N-methyl-D-aspartate induced damage; this protection was more notable as detected by changes in choline acetyltransferase activity. When non-N-methyl-D-aspartate receptor agonists were used as excitotoxins, coinjection of NBQX (25 nmol) resulted in a notable protection against both alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA, 40 nmol) and kainate (10 nmol) induced neurodegeneration. At this concentration, protection was slightly better in AMPA-injected animals (71% protection averaged from choline acetyltransferase and glutamate decarboxylase enzyme activities) as compared to kainate-injected animals (47.5% protection). When a higher concentration of NBQX was tested (40 nmol) the protection against kainate improved to 65% while that against AMPA remained constant (64% protection).(ABSTRACT TRUNCATED AT 250 WORDS)
在本研究中，我们测试了2,3 - 二羟基 - 6 - 硝基 - 7 - 氨磺酰基 - 苯并(f)喹喔啉（NBQX）对向大鼠纹状体注射几种谷氨酸受体激动剂所诱导的兴奋性毒性损伤的神经保护作用。将NBQX与所研究的每种激动剂（1微升）共同注射到纹状体中，并在损伤五天后通过测定纹状体匀浆中的谷氨酸脱羧酶和胆碱乙酰转移酶活性来评估损伤情况。此外，对动物进行经心灌注0.9%生理盐水/4%多聚甲醛，并用甲酚紫对脑冠状切片进行染色以进行组织学分析。我们的结果表明，通过胆碱乙酰转移酶或谷氨酸脱羧酶活性监测，NBQX（25纳摩尔）不能保护免受纹状体内注射200纳摩尔喹啉酸所诱导的损伤。相比之下，相同浓度的NBQX可部分保护免受200纳摩尔N - 甲基 - D - 天冬氨酸诱导的损伤；通过胆碱乙酰转移酶活性的变化检测，这种保护更为显著。当使用非N - 甲基 - D - 天冬氨酸受体激动剂作为兴奋性毒素时，共同注射NBQX（25纳摩尔）可显著保护免受α - 氨基 - 3 - 羟基 - 5 - 甲基 - 4 - 异恶唑丙酸（AMPA，40纳摩尔）和海人酸（10纳摩尔）诱导的神经变性。在此浓度下，与注射海人酸的动物（47.5%保护率）相比，注射AMPA的动物的保护效果稍好（胆碱乙酰转移酶和谷氨酸脱羧酶酶活性平均保护率为71%）。当测试更高浓度的NBQX（40纳摩尔）时，对海人酸的保护率提高到65%，而对AMPA的保护率保持不变（64%保护率）。（摘要截取自250字）
