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Normoglycemia (not hypoglycemia) optimizes outcome from middle cerebral artery occlusion
G M de Courten-Myers1, M Kleinholz, K R Wagner
1Department of Pathology, University of Cincinnati College of Medicine, OH 45267-0533.
Abstract:
We examined the effects of serum glucose concentration during middle cerebral artery (MCA) occlusion in the cat on death rates in animals that died from hemispheric edema and on infarct size in animals that survived. We occluded that MCA permanently in some groups and released the clip after 8 h in others. By injecting or infusing glucose solutions, saline, or insulin, we maintained six animal groups steadily either hyper-, normo-, or slightly hypoglycemic before and for 6 or 8 h after permanent or 8-h temporary MCA occlusion. Studies with these groups revealed a distinct optimal outcome with normoglycemic animals. In three additional groups, we altered the glycemia after permanent occlusion from hyper- to normo- or hypoglycemia and from normo- to hyperglycemia. Two of the three hypoglycemic groups (8-h reversible and permanent hyper- to hypoglycemic occlusions) yielded the worst outcomes in this study, with > 10x larger median infarcts than the best outcome group (normoglycemic permanent occlusion). Hyperglycemia also was detrimental and increased infarct size and mortality after permanent occlusion. Restoring the cerebral blood flow after 8 h of occlusion increased the death rate from hemispheric edema compared with a maintained occlusion. Following permanent MCA occlusion, converting from normo- to hyperglycemia or vice versa yielded outcomes intermediate between a sustained normo- or hyperglycemia. A regression analysis of the normo- and hyperglycemic groups and the two groups with glycemia altered after permanent occlusion showed a significant linear correlation between glycemia level at and 1 h after MCA occlusion and median infarct size.
Insights
Maintaining normal blood glucose levels during middle cerebral artery (MCA) occlusion in cats optimizes outcomes. Both hyperglycemia and hypoglycemia worsen stroke outcomes, increasing infarct size and mortality.
Area of Science:
- Neuroscience
- Cerebrovascular Research
- Metabolic Studies
Background:
- Serum glucose concentration is a critical factor influencing stroke outcomes.
- The impact of glycemic control on ischemic stroke, particularly middle cerebral artery (MCA) occlusion, requires further elucidation.
Purpose of the Study:
- To investigate the effects of pre- and post-occlusion serum glucose levels on mortality and infarct size in a feline model of MCA occlusion.
- To determine the optimal glycemic state for mitigating brain damage following ischemic stroke.
Main Methods:
- Middle cerebral artery (MCA) occlusion was induced permanently or temporarily (8 hours) in cats.
- Animals were maintained in hyperglycemic, normoglycemic, or hypoglycemic states using glucose solutions, saline, or insulin before and after MCA occlusion.
- Mortality rates, causes of death (hemispheric edema), and infarct size were assessed.
Main Results:
- Normoglycemic animals exhibited the best outcomes, with the smallest infarct sizes.
- Both hyperglycemia and hypoglycemia were detrimental, significantly increasing infarct size and mortality.
- Hypoglycemia, particularly when induced after occlusion, led to the largest infarcts (>10x median infarct size compared to normoglycemic group).
- Restoring blood flow after 8 hours of occlusion increased mortality from hemispheric edema compared to sustained occlusion.
Conclusions:
- Normoglycemia is crucial for optimizing outcomes following middle cerebral artery (MCA) occlusion.
- Both high and low blood glucose levels exacerbate ischemic brain injury and increase mortality.
- Glycemic control is a significant therapeutic target for improving stroke recovery.