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(Stroke. 1996;27:1592-1602.)
© 1996 American Heart Association, Inc.

Articles

Effects of Preischemic Hyperglycemia on Brain Damage Incurred by Rats Subjected to 2.5 or5 Minutes of Forebrain Ischemia

Ping-An Li, MD; Tibor Kristian, MD, PhD; Mehrdad Shamloo, MS Bo K. Siesjo, MD, PhD

the Laboratory for Experimental Brain Research, Lund University (P.-A.L., T.K., M.S., B.K.S.), Sweden, and the Institute of Neurobiology, Slovak Academy of Science (T.K.), Kosice, Slovak Republic.

Correspondence to Bo K. Siesjo, Laboratory for Experimental Brain Research, Wallenberg Neuroscience Center, University Hospital, S-221 85 Lund, Sweden.

Background and Purpose The objective of this study was to explore whether preischemic hyperglycemia, which is known to aggravate brain damage due to transient global or forebrain ischemia of intermediate duration (10 to 20 minutes), increases the density of selective neuronal necrosis, as observed primarily in the CA1 sector of the hippocampus after brief periods of forebrain ischemia in rats (2.5 and 5 minutes).

Methods Anesthetized rats were subjected to two-vessel forebrain ischemia of 2.5- or 5-minute duration. Normoglycemic or hyperglycemic rats were either allowed a recovery period of 7 days for histopathological evaluation of neuronal necrosis in the hippocampus, isocortex, thalamus, and substantia nigra or were used for recording of extracellular concentrations of Ca²⁺ ([Ca²⁺]_e), K⁺, or H⁺, together with the direct current (DC) potential.

Results Ischemia of 2.5- or 5-minute duration gave rise to similar damage in the CA1 sector of the hippocampus in normoglycemic and hyperglycemic groups (10% to 15% and 20% to 30% of the total population, respectively). However, in hyperglycemic animals subjected to 2.5 minutes of ischemia, CA1 neurons never depolarized and [Ca²⁺]_e did not decrease. In the 5-minute groups, the total period of depolarization was 2 to 3 minutes shorter in hyperglycemic than in normoglycemic groups. This fact and results showing neocortical, thalamic, and substantia nigra damage in hyperglycemic animals after 5 minutes of ischemia demonstrate that although hyperglycemia delays the onset of ischemic depolarization and hastens repolarization and extrusion of Ca²⁺, it aggravates neuronal damage due to ischemia.

Conclusions These results reinforce the concept that hyperglycemia exaggerates brain damage due to transient ischemia and prove that this exaggeration is observed at the neuronal level. The results also suggest that the concept of the duration of an ischemic transient should be qualified, particularly if ischemia is brief, ie, <10 minutes in duration.

Editorial Comment

Raymond C. Koehler, PhD, Guest Editor

Department of Anesthesiology and Critical Care MedicineThe Johns Hopkins UniversityBaltimore, Md

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