Neuroprotection after focal cerebral ischaemia in hyperglycaemic and diabetic rats.
The effects of acute hyperglycaemia and streptozotocin-induced diabetes on infarct size were measured 48 h after middle cerebral artery occlusion (MCAO) in Fischer 344 rats. Both hyperglycaemia (+46%) and diabetes (+68%) increased infarct volume when compared to normoglycaemic rats. Insulin-treated diabetic rats exhibited an infarct size similar to that observed in normoglycaemic rats. Neuroprotection has been difficult to demonstrate in pathological conditions that increase infarct volume such as chronic arterial hypertension. However, administration of the non-competitive NMDA antagonist, dizocilpine (MK-801), after MCAO, reduced the volume of ischaemic damage (by 33-48%) in all groups. The present findings indicate (a) that the detrimental effects of experimental diabetes on infarct volume are largely attributed to hyperglycaemia; and (b) dizocilpine was as neuroprotective in hyperglycaemia and diabetic conditions as in normoglycaemic rats.
University of Caen, URA 1829 CNRS, Cyceron Research Center, Caen, France.
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Bômont
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MacKenzie
D000818:Animals; D002545:Brain Ischemia / Q000209:etiology / Q000473:pathology*; D002536:Cerebral Arteries / Q000502:physiology; D002544:Cerebral Infarction / Q000473:pathology; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000473:pathology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006943:Hyperglycemia / Q000150:complications* / Q000473:pathology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D013238:Stereotaxic Techniques
D018691:Excitatory Amino Acid Antagonists; D007004:Hypoglycemic Agents; D007328:Insulin; D016291:Dizocilpine Maleate