Published Online
on September 16, 2004

A more recent version of this article appeared on November 1, 2004

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Submitted on July 13, 2004
Accepted on August 9, 2004

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; and 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.

^* To whom correspondence should be addressed. 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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