Prevention of periinfarct direct current shifts with glutamate antagonist NBQX following occlusion of the middle cerebral artery in the rat.

Abstract

The effect of the glutamate (AMPA subtype) receptor antagonist NBQX on periinfarct direct current (DC) shifts and cortical ATP depletion volume was examined in rats subjected to 3 h of occlusion of the middle cerebral artery (MCA). MCA occlusion produced an immediate DC shift in the periphery of the ischemic territory. Vehicle-treated (untreated) animals developed one to five additional DC shifts (median, 2) during the 3-h occlusion time. NBQX treatment (2 x 30 mg/kg i.v. immediately after MCA occlusion and 1 h later) significantly reduced the number of DC deflections (median, 0; range, 0-2; p < 0.05) without changing blood flow in the border zone of the infarct (untreated, 50.6 +/- 10.6%; NBQX-treated: 51.9 +/- 7.7% of control; mean +/- SD). NBQX treatment significantly decreased the cortical volume of ATP depletion (untreated, 75.3 +/- 11.4 mm3; NBQX-treated, 47.9 +/- 10.1 mm3; p < 0.05). Moreover, a significant linear relationship between the number of periinfarct DC shifts and the volume of cortical ATP depletion was obtained (y = 38.3 + 9.4x; r = 0.866; p < 0.001). The reduction of brain infarct volume by NBQX treatment is explained by the suppression of DC shifts and the decrease of metabolic workload in hemodynamically compromised cortex.