Blockade of AMPA receptors reduces brain edema following opening of the blood-brain barrier.

The aim of our study was to evaluate whether blockade of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors could reduce brain edema in two experimental models of edema following opening of the blood-brain barrier (BBB). The brain specific gravity was determined 2 h after opening the BBB by a 30-s infusion of protamine sulfate (10 mg in 200 microliters 0.9% NaCl) or arabinose (1.5 or 1.8 mol/L, 0.06 ml.s-1) into the right internal carotid artery. Cisternal CSF was withdrawn for albumin determination before the carotid infusion and before killing 2 h later. After infusion of protamine sulfate or arabinose, CSF albumin increased in all groups. The brain specific gravity was significantly lower in the right than in the left (control) frontal, parietal, and occipital cortex and striatum. NBQX (2,3-dihydroxy-6-nitro-7-sulfamoylbenxo(F)quinoxaline), an AMPA receptor antagonist, given intravenously 10 min after opening the BBB (5 mg/kg), significantly increased the specific gravity in the treated rats (p < 0.01 for the difference from control rats) without reducing CSF albumin or albumin extravasation in the brain as evaluated with Evans blue. We hypothesize that intracerebral (glial?) AMPA receptors may play a role in brain edema following opening of the BBB.