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Infarct rim: effect of hyperglycemia on direct current potential and [14C]2-deoxyglucose phosphorylation
Abstract:
Focal ischemia was produced by occlusion of the right middle cerebral artery (MCA) in normo- and hyperglycemic rats. In the cortical infarct rim, regional [14C]2-deoxyglucose [( 14C]2-DG) phosphorylation was correlated to spontaneous transient changes in extracellular potassium recorded as direct current (DC) potential deflections. In normoglycemic rats the DC potential showed transient but recurrent deflections in the first hours following MCA occlusion. The 2-DG phosphorylation was elevated by 200% in the same area. In contrast, hyperglycemic rats had no, or a single, deflection of the DC potential in the rim, and the 2-DG phosphorylation remained normal. The same pattern was obtained by application of 3 M KCl to the exposed cortex. In normoglycemia potassium application resulted in recurrent deflections of the DC potential, and 2-DG phosphorylation increased in most parts of the hemisphere. Hyperglycemic animals had a nearly stable DC potential, and 2-DG phosphorylation increased only in the tissue area situated directly below the site of potassium application. The results indicate that metabolism in the cortical infarct rim is stimulated by spontaneous and recurrent changes in extracellular potassium--a phenomenon that may be related to spreading depression--and that the metabolism remained normal in the same area in hyperglycemic animals owing to an inhibition of transient increases of extracellular potassium.
Insights
Hyperglycemia impairs brain metabolism during stroke by inhibiting extracellular potassium changes. This suggests that managing blood sugar levels is crucial for protecting brain tissue during focal ischemia.
Area of Science:
- Neuroscience
- Cerebrovascular Research
- Metabolic Neuroscience
Background:
- Focal ischemia, such as middle cerebral artery (MCA) occlusion, triggers complex metabolic and ionic changes in the brain.
- Extracellular potassium shifts are implicated in neuronal activity and metabolic responses following ischemic events.
- The impact of hyperglycemia on these dynamic processes in the ischemic penumbra remains incompletely understood.
Purpose of the Study:
- To investigate the role of extracellular potassium dynamics in regulating regional glucose metabolism within the cortical infarct rim.
- To determine how hyperglycemia influences these potassium-mediated metabolic changes during focal cerebral ischemia.
Main Methods:
- Induction of focal cerebral ischemia via right MCA occlusion in normoglycemic and hyperglycemic rats.
- Measurement of regional [14C]2-deoxyglucose ([14C]2-DG) phosphorylation as an index of glucose metabolism.
- Recording of spontaneous transient changes in extracellular potassium using direct current (DC) potential deflections.
- Application of exogenous potassium (3 M KCl) to assess its effects on DC potentials and metabolism.
Main Results:
- In normoglycemic rats, MCA occlusion led to recurrent DC potential deflections and a 200% increase in [14C]2-DG phosphorylation in the infarct rim.
- Hyperglycemic rats exhibited minimal DC potential deflections and normal [14C]2-DG phosphorylation in the same region.
- Exogenous potassium application induced DC deflections and increased metabolism in normoglycemic rats, while its effect was significantly blunted in hyperglycemic animals.
Conclusions:
- Spontaneous, recurrent extracellular potassium fluctuations, potentially related to spreading depression, stimulate glucose metabolism in the ischemic cortical rim.
- Hyperglycemia inhibits these critical potassium transients, leading to preserved normal metabolism in the infarct area.
- These findings highlight a mechanism by which hyperglycemia exacerbates brain damage in stroke by disrupting neuroprotective metabolic responses.
