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 brain damage. In normoglycemic animals this damage usually consists of selective neuronal necrosis (SNN), and is largely confined to the lateral caudoputamen. In hyperglycemic subjects damage occurs more rapidly, involves also neocortical areas, and is often of the pan-necrotic type ('infarction'). Since experiments on forebrain ischemia of 30 min duration suggest that microcirculatory compromise develops during recirculation, we studied whether focal ischemia of the same duration, followed by reperfusion for 1, 2 or 4 h, leads to microcirculatory dysfunction. To test this possibility, we fixed the tissue by perfusion and counted the number of formed elements (leukocytes, macrophages and erythrocytes) in capillaries and postcapillary venules. Furthermore, capillary 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 caudoputamen of normoglycemic animals. Hyperglycemic, but not normoglycemic, animals showed pan-necrotic lesions ('infarction') after 4 h of recirculation. As a result, the total volume of tissue damage (SNN plus infarction) was larger in hyper- than in normoglycemic animals at 2 and 4 h of recirculation. In addition, hyperglycemic animals showed involvement of neocortex which increased with the time of reperfusion. In the ischemic hemisphere, between 5 and 10% of counted capillaries contained formed elements. However, since hyperglycemic animals contained an equal (or smaller) amount of cells the results did not suggest that 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 aggravation of focal ischemic damage by hyperglycemia is due to obstruction of microvessel by swelling or leukocyte adherence.
Li
P A
PA
Center for the Study of Neurological Diseases, Queen's Neuroscience Institute, Queen's Medical Center, Honolulu, Hawaii, USA.
Gisselsson
L
L
Keuker
J
J
Vogel
J
J
Smith
M L
ML
Kuschinsky
W
W
Siesjö
B K
BK
D000818:Animals; D001157:Arterial Occlusive Diseases / Q000150:complications*; D001925:Brain Damage, Chronic / Q000209:etiology*; D002545:Brain Ischemia / Q000150:complications*; D002196:Capillaries / Q000503:physiopathology; D002536:Cerebral Arteries; D002540:Cerebral Cortex / Q000473:pathology; D002544:Cerebral Infarction / Q000473:pathology; D003251:Constriction, Pathologic; D003342:Corpus Striatum / Q000473:pathology; D006943:Hyperglycemia / Q000150:complications*; D008297:Male; D009336:Necrosis; D009474:Neurons / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D014654:Vascular Patency / Q000502:physiology