2,3-Dihydroxy-6-nitro-7-sulfamoylbenzo(F)-quinoxaline (
NBQX), an alpha-amino-3-hydroxy-5-methyl-4-isoxazole
propionic acid (
AMPA) receptor antagonist, has been reported to provide neuronal protection after global
ischemia. The objectives of this study were to evaluate the
neuroprotective effects of
NBQX initiated after focal cortical
ischemia and to validate a method for measuring functional outcome in this model. Male spontaneously hypertensive rats (SHRs) were exposed to various durations of transient or permanent tandem middle cerebral artery (MCA) occlusion. Studies compared motor performance using balance beam and prehensile-
traction tests,
calcium-
calmodulin (Ca-CaM) binding by immunohistochemistry, and
infarct volume between
NBQX-treated animals [intravenous (i.v.) 5 mg/kg/h x 6 h or intraperitoneal (i.
p.) 30 mg/kg q 30 min x 3 begun postischemia] and controls. All ischemic groups performed less well than
sham-operated controls on the motor performance tasks in proportion to the severity of
ischemia. No significant improvement in motor performance was noted in the
NBQX-treated versus the control animals after 1 h or permanent MCA/CCA occlusion. Treatment with
NBQX (i.v. or i.p. dosing) did not reduce Ca-CaM binding after 1 h of occlusion with 1 h of reperfusion or after 2 h of occlusion. Similarly, there was no reduction in
infarct size between
NBQX-treated and control animals after 24 h of permanent MCA/CCA occlusion (74.6 +/- 7.1 vs. 80.1 +/- 6.0 ml; ns) or after 1 h of occlusion with 23 h of reperfusion (55.1 +/- 4.4 vs. 47.4 +/- 6.2 ml; ns).(ABSTRACT TRUNCATED AT 250 WORDS)