HYPERGLYCEMIA-EXAGGERATED ISCHEMIC BRAIN-DAMAGE FOLLOWING 30 MIN OF MIDDLE CEREBRAL-ARTERY OCCLUSION IS NOT DUE TO CAPILLARY OBSTRUCTION

Transient focal ischemia of brief duration (15-30 min) gives rise to b rain damage. In normoglycemic animals this damage usually consists of selective neuronal necrosis (SNN), and is largely confined to the late ral caudoputamen. In hyperglycemic subjects damage occurs more rapidly , involves also neocortical areas, and is often of the pan-necrotic ty pe ('infarction'). Since experiments on forebrain ischemia of 30 min d uration suggest that microcirculatory compromise develops during recir culation, we studied whether focal ischemia of the same duration, foll owed by reperfusion for 1, 2 or 4 h, leads to microcirculatory dysfunc tion. To test this possibility, we fixed the tissue by perfusion and c ounted the number of formed elements (leukocytes, macrophages and eryt hrocytes) in capillaries and postcapillary venules. Furthermore, capil lary patency was evaluated following in vivo injection of Evan's blue. Histopathological examination of tissue fixed by perfusion after 1, 2 and 4 h of recirculation showed an increasing density of SNN in the c audoputamen of normoglycemic animals. Hyperglycemic, but not normoglyc emic, animals showed pan-necrotic lesions ('infarction') after 4 h of recirculation. As a result, the total volume of tissue damage (SNN plu s infarction) was larger in hyper- than in normoglycemic animals at 2 and 4 h of recirculation. In addition, hyperglycemic animals showed in volvement of neocortex which increased with the time of reperfusion. I n the ischemic hemisphere, between 5 and 10% of counted capillaries co ntained formed elements. However, since hyperglycemic animals containe d an equal (or smaller) amount of cells the results did not suggest th at capillary 'plugging' could explain the aggravated damage. Moreover, both normo- and hyperglycemic animals showed close to 100% capillary patency. The results thus fail to support the notion that the aggravat ion of focal ischemic damage by hyperglycemia is due to obstruction of microvessel by swelling or leukocyte adherence. (C) 1998 Elsevier Sci ence B.V. All rights reserved.