The effect of global brain ischemia in normal and diabetic animals: the influence of calcium channel blockers.
Diabetes with hypertension is characterized by increased cerebrovascular pathology and poorer outcomes following stroke. In this study we evaluated the effect of global brain ischemia on brain metabolic parameters in normal and diabetic rats treated with a dihydropyridine calcium antagonist, felodipine. Normal and diabetic rats were treated daily with felodipine (5 mg/kg) or saline. After 4 wk global ischemia was produced by occluding the carotid arteries for 1 h. In other groups the occlusion was removed and the animals were allowed to reperfuse for an additional 2 h. Following 1 h global ischemia, with or without reperfusion, the animals and controls were killed by decapitation. Cerebral water, lactate, ATP, and glutamate were measured. Glo-bal ischemia with or without reperfusion increased cerebral water and lactate, but decreased ATP. Treatment with felodipine decreased lactate, but increased water content. Ischemia in diabetics with or without reperfusion decreased water and lactate. Treated diabetics had higher ATP levels after reperfusion. Glutamate levels were increased in diabetics and were further increased by treatment. We conclude that the enhanced CNS damage following cerebral ischemia in diabetes is not correlated with ATP or lactate levels and may be mediated in part by increased glutamate. Calcium channel antagonist may augment this process.
Levy
Joseph
J
Department of Medicine, Wayne State University School of Medicine, Detroit, MI 48201-1928, USA.
Zhu
Zhengxian
Z
Dunbar
Joseph C
JC
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology; D002545:Brain Ischemia / Q000150:complications / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism*; D015736:Felodipine / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000150:complications / Q000378:metabolism*; D014867:Water / Q000378:metabolism
D002121:Calcium Channel Blockers; D014867:Water; D019344:Lactic Acid; D018698:Glutamic Acid; D000255:Adenosine Triphosphate; D015736:Felodipine; D002118:Calcium