Cerebral Blood Flow and Cerebral Edema in Rats With Diabetic Ketoacidosis
Natalie Yuen 1 ,
Steven E. Anderson 1 ,
Nicole Glaser 2 ,
Daniel J. Tancredi 2 and
Martha E. O'Donnell 1
1 Department of Physiology and Membrane Biology, University of California, Davis, California
2 Department of Pediatrics, University of California, Davis, California
Corresponding author: Dr. Martha E. O'Donnell, meodonnell{at}ucdavis.edu
Abstract
OBJECTIVE— Cerebral edema (CE) is a potentially life-threatening complication of diabetic ketoacidosis (DKA) in children. Osmotic fluctuations
during DKA treatment have been considered responsible, but recent data instead suggest that cerebral hypoperfusion may be
involved and that activation of cerebral ion transporters may occur. Diminished cerebral blood flow (CBF) during DKA, however,
has not been previously demonstrated. We investigated CBF and edema formation in a rat model of DKA and determined the effects
of bumetanide, an inhibitor of Na-K-Cl cotransport.
RESEARCH DESIGN AND METHODS— Juvenile rats with streptozotocin-induced DKA were treated with intravenous saline and insulin, similar to human treatment
protocols. CBF was determined by magnetic resonance (MR) perfusion–weighted imaging before and during treatment, and CE was
assessed by determining apparent diffusion coefficients (ADCs) using MR diffusion–weighted imaging.
RESULTS— CBF was significantly reduced in DKA and was responsive to alterations in pCO 2 . ADC values were reduced, consistent with cell swelling. The reduction in ADCs correlated with dehydration, as reflected
in blood urea nitrogen concentrations. Bumetanide caused a rapid rise in ADCs of DKA rats without significantly changing CBF,
while saline/insulin caused a rapid rise in CBF and a gradual rise in ADCs. DKA rats treated with bumetanide plus saline/insulin
showed a trend toward more rapid rise in cortical ADCs and a larger rise in striatal CBF than those observed with saline/insulin
alone.
CONCLUSIONS— These data demonstrate that CE in DKA is accompanied by cerebral hypoperfusion before treatment and suggest that blocking
Na-K-Cl cotransport may reduce cerebral cell swelling.
Footnotes
Published ahead of print at http://diabetes.diabetesjournals.org on 15 July 2008.
Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work
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Cerebral Blood Flow and Cerebral Edema in Rats With Diabetic Ketoacidosis

10.2337/db07-1410