What causes infarction in ischemic brain?: The Robert Wartenberg Lecture.

Area of Science:

• Neuroscience
• Cerebrovascular Medicine
• Metabolic Encephalopathy

Background:

• Cardiovascular and hematologic treatments have improved cerebral vascular disease outcomes.
• Brain carbohydrate metabolism, specifically lactate levels, is increasingly recognized as a factor in ischemic brain injury.

Purpose of the Study:

• To investigate the role of brain lactate levels in determining the outcome of cerebral ischemia.
• To explore the protective potential of astrocytes and the impact of high lactate on them.

Main Methods:

• Comparative analysis of ischemic brain tissue with varying lactate levels.
• Histological examination to assess neuronal, astrocytic, and endothelial cell damage.
• Evaluation of cerebral edema development post-ischemia.

Main Results:

• Ischemia with brain lactate levels >16 mmol/kg results in tissue infarction, including neuronal, astrocytic, and endothelial necrosis.
• Lower lactate levels during equivalent ischemia lead to selective neuronal damage, sparing astrocytes and endothelia, and preventing edema.
• Astrocytes demonstrate a protective role against anoxia but are vulnerable to high lactate concentrations.

Conclusions:

• Brain lactate levels are critical determinants of ischemic brain injury severity.
• Managing blood sugar to control brain lactate may mitigate ischemic brain damage and reduce cerebral infarction risk.
• Astrocytes play a vital role in brain defense during anoxia but require protection from excessive lactate accumulation.