title: 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.
authors.affiliation: Max-Planck-Institute for Neurological Research, Department of Experimental Neurology, Köln (Lindenthal), Germany.
authors.forename: G
authors.initials: G
authors.lastname: Mies
authors.forename: K
authors.initials: K
authors.lastname: Kohno
authors.forename: K A
authors.initials: KA
authors.lastname: Hossmann
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D002536:Cerebral Arteries / Q000503:physiopathology; D002544:Cerebral Infarction / Q000503:physiopathology*; D004569:Electroencephalography; D004594:Electrophysiology; D008297:Male; D011810:Quinoxalines / Q000494:pharmacology*; D051381:Rats; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors*
chemical_list: D011810:Quinoxalines; D018091:Receptors, AMPA; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline