2,3-Dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline protects against both AMPA and kainate-induced lesions in rat striatum in vivo.
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)
Massieu
L
L
Departamento de Neurociencias, Universidad Nacional Autónoma de México, D.F., México.
Tapia
R
R
D000818:Animals; D015415:Biomarkers; D002795:Choline O-Acetyltransferase / Q000032:analysis; D003342:Corpus Striatum / Q000187:drug effects* / Q000473:pathology; D005968:Glutamate Decarboxylase / Q000032:analysis; D007608:Kainic Acid / Q000037:antagonists & inhibitors* / Q000633:toxicity; D008297:Male; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors / Q000633:toxicity; D009410:Nerve Degeneration / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000032:analysis; D011810:Quinoxalines / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D017470:Receptors, Glutamate / Q000187:drug effects* / Q000502:physiology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000037:antagonists & inhibitors* / Q000633:toxicity
D015415:Biomarkers; D009419:Nerve Tissue Proteins; D011810:Quinoxalines; D017470:Receptors, Glutamate; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D002795:Choline O-Acetyltransferase; D005968:Glutamate Decarboxylase; D007608:Kainic Acid