Cortical spreading depolarization in patients with malignant hemispheric stroke

• Applicant: Professor Dr. Johannes Woitzik
• Subject Area: Clinical Neurology; Neurosurgery and Neuroradiology
• Term: from 2010 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 178961426

Cortical spreading depolarization (CSD) describes a wave of neuronal and astroglial mass-depolarization that propagates in the cortex at a velocity of 2 - 8 mm/min and leads to significant ion-shifts. Recovery from CSD is energy dependent. Therefore, CSD is physiologically coupled to vasodilation and hyperperfusion in healthy brain tissue. In damaged tissue, however, CSD is frequently associated with hypoperfusion (=inverse flow coupling). Together with the metabolic impairment, CSD might exacerbate brain damage. Early after onset following experimental ischemia, the number of spontaneous CSDs are proportional to infract progression. In a prospective study we recently demonstrated that delayed infarct progression (>24 hours after stroke onset; median progression volume 43 cm3) occurred in 50% of patients with malignant hemispheric stroke. Delayed infarct progression was also associated with significant metabolic impairment within the peri-infarct tissue. Further, CSDs with hyper- and hypoemic flow-coupling were detected with high incidence. To what extend these relatively delayed occurring CSDs (>24 hours after stroke onset) may be associated with metabolic impairment and delayed infarct progression requires further investigation. Therefore, in this translational clinical and experimental research project we would like to investigate to what extent spontaneous CSDs after malignant hemispheric stroke are associated with metabolic impairment and delayed (>24 hours after onset) infarct progression. Within the clinical part, patients with malignant hemispheric stroke will undergo combined intraoperative laser speckle imaging and spectroscopic optical imaging in order to follow CSDs and associated flow- and metabolic changes. Thereafter, an opto-electrode, microdialysis- and tissue oxygen-probe will be placed over the peri-infarct tissue to follow CSD-associated flow, electrocorticographic, tissue oxygen and metabolic changes during the first 5 days after surgery. Delayed infarct progression will be determined from serial magnetic resonance imaging and volumetric analysis. Experimentally, we will examine whether delayed occurring CSDs (>24 hours after stroke onset) in mice with focal ischemia are associated with stroke progression and whether pharmacological blockade or modulation of flow coupling will impede stroke progression.

• DFG Programme: Research Grants