A glycine site antagonist, ZD9379, reduces number of spreading depressions and infarct size in rats with permanent middle cerebral artery occlusion

Stroke; a Journal of Cerebral Circulation
T TatlisumakM Fisher

Abstract

Spreading depressions (SDs) occur in experimental focal ischemia and contribute to lesion evolution. N-Methyl-D-aspartate (NMDA) antagonists inhibit SDs and reduce infarct size. The glycine site on the NMDA receptor complex offers a therapeutic target for acute focal ischemia, potentially devoid of many side effects associated with competitive and noncompetitive NMDA antagonists. We evaluated the effect of the glycine antagonist ZD9379 on SDs and brain infarction. Male Sprague-Dawley rats (n = 18) weighing 290 to 340 g undergoing permanent middle cerebral artery occlusion (MCAO) were randomly and blindly assigned to receive drug or placebo: group 1 (pre-MCAO treatment group; n=5), a 5-mg/kg bolus of ZD9379 over 5 minutes followed by 5 mg/kg per hour drug infusion for 4 hours beginning 30 minutes before MCAO; group 2 (post-MCAO treatment group; n=7), a 5-mg/kg bolus of ZD9379 30 minutes after MCAO followed by 5 mg/kg per hour drug infusion for 4 hours; and group 3 (control group; n=6), vehicle for 5 hours beginning 30 minutes before MCAO. SDs were monitored electrophysiologically for 4.5 hours after MCAO by continuous recording of cortical DC potentials and electrocorticogram. Infarct volume was measured 24 hours after MCAO by 2...Continue Reading

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Citations

Nov 8, 2001·European Journal of Pharmacology·C G Parsons
Aug 23, 2003·European Journal of Medicinal Chemistry·Michaela Jansen, Gerd Dannhardt
Mar 20, 2010·Experimental & Translational Stroke Medicine·Aysan Durukan, Turgut Tatlisumak
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Apr 21, 2018·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Anna KlassEdgar Santos
Jan 16, 2008·Physiological Reviews·Tihomir Paul Obrenovitch

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