Abstract TP92: Early Hyperacute Ion Dysregulation Following A Temporary Large Vessel Occlusion Stroke

Introduction: Ion dysregulation is a hallmark of energy failure after onset of ischemic stroke. To better understand the nature of the ion concentration changes in the early hyperacute phase after stroke onset we have quantitatively imaged the trace element distribution in the stroke lesion territory after a 30-minute temporary large vessel occlusion stroke. Methods: A temporary large vessel occlusion stroke was generated with the middle cerebral artery occlusion (MCAO) mouse model (insertion of an occluding filament via the ECA) with reperfusion after 30 minutes (occluding filament withdrawn). C57BL/6 mice (5 per time point) were euthanized at 5-, 30-, 60-, 90-, and 120-minutes post reperfusion. Shams included all surgical procedures, however the occluding filament was withdrawn immediately after insertion. Heads were immediately frozen post mortem and sectioned for trace element mapping. Quantitative X-ray fluorescence microscopy was performed at the Stanford Synchrotron Radiation Lightsource. Results: Loss of potassium is observed throughout the affected tissue at all post-reperfusion time points, with most of the initial loss occurring in the 30-minutes prior to reperfusion. Loss of essential zinc began to be observed 1-hour post reperfusion. No significant elevations in chlorine or calcium were observed during the early hyperacute phase. At subsequent post reperfusion time points the lesion (as defined by diminished potassium) grew steadily for 90-minutes. After 90-minutes post reperfusion some lesions demonstrated a distinct pattern consistent with a central infarct core surrounded by an ischemic penumbra. Conclusions: At all early hyperacute time points the stroke lesion demonstrated on-going potassium dysregulation, despite reperfusion. The loss of potassium was a bulk phenomenon in the tissue. Potassium is essential for maintenance of neuronal membrane potential and therefore function. Restoration of normal blood flow is insufficient to protect the brain from the enduring reduction in vital potassium levels or expansion of the region of ion dysregulation. The lack of available potassium within the affected tissue may hinder recovering neuronal cells from restoring action potentials, even after tissue perfusion is restored.