Prevention of Periinfarct Direct Current Shifts with Glutamate Antagonist NBQX following Occlusion of the Middle Cerebral Artery in the Rat

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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 × 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.

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