EFFECTS OF PREISCHEMIC HYPERGLYCEMIA ON BRAIN-DAMAGE INCURRED BY RATSSUBJECTED TO 2.5 OR 5 MINUTES OF FOREBRAIN ISCHEMIA

Background and Purpose The objective of this study was to explore whet her preischemic hyperglycemia, which is known to aggravate brain damag e due to transient global or forebrain ischemia of intermediate durati on (10 to 20 minutes), increases the density of selective neuronal nec rosis, as observed primarily in the CA1 sector of the hippocampus afte r brief periods of forebrain ischemia in rats (2.5 and 5 minutes). Met hods Anesthetized rats were subjected to two-vessel forebrain ischemia of 2.5- or 5-minute duration. Normoglycemic or hyperglycemic rats wer e either allowed a recovery period of 7 days for histopathological eva luation of neuronal necrosis in the hippocampus, isocortex, thalamus, and substantia nigra or were used for recording of extracellular conce ntrations of Ca2+ ([Ca2+](e)), K+, or H+, together with the direct cur rent (DC) potential. Results Ischemia of 2.5- or 5-minute duration gav e rise to similar damage in the CA1 sector of the hippocampus in normo glycemic and hyperglycemic groups (10% to 15% and 20% to 30% of the to tal population, respectively). However, in hy perglycemic animals subj ected to 2.5 minutes of ischemia, CA1 neurons never depolarized and [C a2+](e) did not decrease. In the 5-minute groups, the total period of depolarization was 2 to 3 minutes shorter in hyperglycemic than in nor moglycemic 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 Thes e results reinforce the concept that hyperglycemia exaggerates brain d amage due to transient ischemia and prove that this exaggeration is ob served at the neuronal level. The results also suggest that the concep t of the duration of an ischemic transient should be qualified, partic ularly if ischemia is brief, ie, < 10 minutes in duration.