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(Stroke. 2004;35:2587.)
© 2004 American Heart Association, Inc.

Original Contributions

Glutamate Receptor Blockade Attenuates Glucose Hypermetabolism in Perihematomal Brain After Experimental Intracerebral Hemorrhage in Rat

Timothy D. Ardizzone, PhD; Aigang Lu, MD MS; Kenneth R. Wagner, PhD; Yang Tang, MD PhD; Ruiqiong Ran, MD PhD Frank R. Sharp, MD

From the Departments of Neurology, Pediatrics, and the Neurosciences Graduate Program (T.D.A., A.L., K.R.W., Y.T., R.R., F.R.S.), University of Cincinnati College of Medicine, Ohio; the Medical Research Service (K.R.W.), Department of Veterans Affairs Medical Center, Cincinnati, Ohio; and Medical Investigation of Neurodevelopmental Disorders (MIND) Institute and Department of Neurology (A.L., Y.T., R.R., F.R.S.), University of California at Davis, Sacramento, Calif.

Correspondence to Dr Frank R. Sharp, MIND Institute and Department of Neurology, University of California at Davis Medical Center, 2805 50th St, Room 2416, Sacramento, CA 95817. E-mail frank.sharp{at}ucdmc.ucdavis.edu

Background and Purpose— Intracerebral hemorrhage has no effective treatment. The delayed appearance of edema, apoptosis, and inflammation in perihematomal brain suggests that these events may be targets for therapeutic intervention. To develop successful treatments, we must learn more about the effects of hemorrhage on brain tissue. In this study, we investigated the acute metabolic effects of intrastriatal hemorrhage in rat brain.

Methods— Lysed blood or saline (50 µL each) was injected into the striatum of male Sprague-Dawley rats. The rats recovered for 1 to 72 hours before injection of [¹⁴C]-2-deoxyglucose (intraperitoneally) 30 minutes before decapitation. Animals were pretreated with the N-methyl-D-aspartate (NMDA) and -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor antagonists dizolcilpine maleate (MK-801; 1 mg/kg) or 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo[f]quinoxaline (NBQX; 30 mg/kg), or saline vehicle. Additional animals received intrastriatal injections of glutamate (1.0 mmol/L), NMDA (1.0 mmol/L), or AMPA (0.1 mmol/L) in the place of blood. Semiquantitative autoradiographs from the brains were analyzed to determine the effects of hemorrhage on relative glucose metabolism.

Results— We found an acute phase of increased [¹⁴C]-2-deoxyglucose uptake in the perihematomal region that peaks 3 hours after lysed blood injection. Saline injections had no effect on striatal glucose utilization. The increased [¹⁴C]-2-deoxyglucose uptake produced by the hemorrhages was blocked by pretreatment with MK-801 and NBQX. Glutamate injections alone had no effect on striatal metabolism, whereas NMDA and AMPA injections increased [¹⁴C]-2-deoxyglucose uptake.

Conclusions— The data imply that glutamate activation of NMDA or AMPA receptors increases glucose metabolism in perihematomal brain at early times after intracerebral hemorrhage. This may provide a possible target for the treatment of intracerebral hemorrhage.

Key Words: intracerebral hemorrhage • MK-801 • stroke, hemorrhagic

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