This Article Full Text Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Warner, D. S. Articles by McAllister, A. M. Search for Related Content PubMed PubMed Citation Articles by Warner, D. S. Articles by McAllister, A. M.

(Stroke. 1995;26:655-660.)
© 1995 American Heart Association, Inc.

Articles

Temporal Thresholds for Hyperglycemia-Augmented Ischemic Brain Damage in Rats

David S. Warner, MD; Michael M. Todd, MD; Franklin Dexter, MD, PhD; Paula Ludwig Alice M. McAllister

From the Department of Anesthesiology, Duke University Medical Center, Durham, NC (D.S.W., P.L.), and the Department of Anesthesia, University of Iowa, Iowa City (M.M.T., F.D., A.M.M.).

Correspondence to David S. Warner, MD, Department of Anesthesiology, Box 3094, Duke University Medical Center, Durham, NC 27710.

Background and Purpose Although acute hyperglycemia is known to increase global ischemic brain damage, the duration of ischemia necessary to elicit such an effect is unknown. Accordingly, an experiment was performed to determine the duration of forebrain ischemia at which hyperglycemia becomes a factor in histological and behavioral outcome in rats.

Methods Fasted rats were anesthetized and prepared for forebrain ischemia. Before ischemia, rats received either intravenous saline (plasma glucose, 112±18 mg/dL) or glucose (plasma glucose, 343±50 mg/dL). After 4, 8, 12, or 15 minutes of ischemia (n=12), recovery was allowed. Rats surviving 7 days underwent evaluation of motor function and then histological analysis of damage in the caudate putamen, hippocampal CA1, and substantia nigra pars reticulata.

Results After 4 minutes of ischemia, damage was present in all structures. Only in the caudate putamen was hyperglycemia associated with worsened damage, but this did not result in seizures or death. After 8 minutes of ischemia, seizures occurred in 33% of hyperglycemic rats, and a hyperglycemic effect on damage in the CA1 and substantia nigra pars reticulata was observed. No seizures or mortality occurred in normoglycemic rats regardless of duration of ischemia. Longer durations of ischemia resulted in an increased incidence of seizures and mortality in hyperglycemic rats only. Among surviving rats, motor function was worsened in hyperglycemic rats after 12 minutes of ischemia.

Conclusions Hyperglycemia-augmented brain damage is evident after global ischemic insults as brief as 4 minutes and becomes critical to survival after 8 minutes of ischemia.

Key Words: cerebral ischemia • hyperglycemia • neuronal damage • rats

This article has been cited by other articles:

				K. S Lewis, S. L Kane-Gill, M. B. Bobek, and J. F Dasta Intensive Insulin Therapy for Critically Ill Patients Ann. Pharmacother., July 1, 2004; 38(7): 1243 - 1251. [Abstract] [Full Text] [PDF]

				B. P. Conroy, M. R. Grafe, L. W. Jenkins, A. H. Vela, C. Y. Lin, D. S. DeWitt, and W. E. Johnston Histopathologic consequences of hyperglycemic cerebral ischemia during hypothermic cardiopulmonary bypass in pigs Ann. Thorac. Surg., April 1, 2001; 71(4): 1325 - 1334. [Abstract] [Full Text] [PDF]

				Y. Morimoto, Y. Morimoto, D. S. Warner, R. D. Pearlstein, and J. P. Muizelaar Acute Changes in Intracranial Pressure and Pressure-Volume Index After Forebrain Ischemia in Normoglycemic and Hyperglycemic Rats Stroke, August 1, 1996; 27(8): 1405 - 1410. [Abstract] [Full Text]