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J Neurosci Res. 2001 Dec 1;66(5):782-9.

Preischemic hyperglycemia-aggravated damage: evidence that lactate utilization is beneficial and glucose-induced corticosterone release is detrimental.

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Brain Attack Research Laboratory, Department of Anesthesiology, University of Louisville School of Medicine, Louisville, KY 40292, USA.


Aerobic lactate utilization is crucial for recovery of neuronal function posthypoxia in vitro. In vivo models of cerebral ischemia pose a conceptual challenge when compared to in vitro models. First, the glucose paradox of cerebral ischemia, namely, the aggravation of delayed neuronal damage by preischemic hyperglycemia, cannot be reproduced in vitro. Second, in vitro elevated glucose levels protect against ischemic (hypoxic) damage, an outcome that has seldom been reproduced in vivo. Employing a rat model of cardiac-arrest-induced transient global cerebral ischemia (TGI), we found that hyperglycemic conditions, when induced 120-240 min pre-TGI, significantly reduced post-TGI neuronal damage as compared to normoglycemic conditions. In contrast, hyperglycemia, when induced 15-60 min pre-TGI, significantly aggravated post-TGI neuronal damage. Brain lactate levels in rats loaded with glucose either 15 min or 120 min pre-TGI were significantly and equally higher than those of control, saline-injected rats. The beneficial effect of 120 min pre-TGI glucose loading was abolished by lactate transport inhibition. A significant increase in blood corticosterone (CT) levels was observed upon glucose loading that peaked at 15-30 min and returned to baseline levels by 60-120 min. When rats loaded with glucose 15 min pre-TGI were treated with metyrapone, a CT synthesis inhibitor, a significantly lower degree of delayed neuronal damage in comparison to both untreated, 15 min glucose-loaded rats and normoglycemic, control rats was observed. Thus, although elevated levels of brain lactate cannot explain the glucose paradox of cerebral ischemia, hyperglycemia-induced, short-lived elevation in CT blood levels could. More importantly, lactate appears to play a crucial role in improving postischemic outcome.

[Indexed for MEDLINE]

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