Bench-to-bedside review: a possible resolution of the glucose paradox of cerebral ischemia.
The glucose paradox of cerebral ischemia (namely, the aggravation of delayed ischemic neuronal damage by preischemic hyperglycemia) has been promoted as proof that lactic acidosis is a detrimental factor in this brain disorder. Recent studies, both in vitro and in vivo, have demonstrated lactate as an excellent aerobic energy substrate in the brain, and possibly a crucial one immediately postischemia. Moreover, evidence has been presented that refutes the lactic acidosis hypothesis of cerebral ischemia and thus has questioned the traditional explanation given for the glucose paradox. An alternative explanation for the aggravating effect of preischemic hyperglycemia on the postischemic outcome has consequently been offered, according to which glucose loading induces a short-lived elevation in the release of glucocorticoids. When an episode of cerebral ischemia in the rat coincided with glucose-induced elevated levels of corticosterone (CT), the main rodent glucocorticoid, an aggravation of the ischemic outcome was observed. Both the blockade of CT elevation by chemical adrenalectomy with metyrapone or the blockade of CT receptors in the brain with mifepristone (RU486) negated the aggravating effect of preischemic hyperglycemia on the postischemic outcome.
Schurr
Avital
A
Brain Attack Research Laboratory, Department of Anesthesiology, University of Louisville School of Medicine, Louisville, KY 40292, USA. a0schu01@gwise.louisvile.edu
D000140:Acidosis, Lactic / Q000150:complications* / Q000378:metabolism; D000818:Animals; D002545:Brain Ischemia / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D003345:Corticosterone / Q000378:metabolism*; D006727:Hormone Antagonists / Q000627:therapeutic use*; D006801:Humans; D006943:Hyperglycemia / Q000150:complications* / Q000378:metabolism; D015735:Mifepristone / Q000627:therapeutic use*; D051381:Rats
D006727:Hormone Antagonists; D015735:Mifepristone; D003345:Corticosterone