Quantitative Imaging of the Heterogeneity of Brain Potassium Depletion in Experimental Focal Ischemia

Abstract BACKGROUND With few exceptions, pathological progression in ischemic stroke is presumed to occur uniformly within the ischemic core region. These exceptions include edema formation, brain tissue [Na + ] increase, and the qualitative visually observed decrease of brain tissue [K + ], [K + ] br , all of which occur in peripheral regions of the ischemic core. We hypothesize that [K + ] br depletion and egress occur heterogeneously in the peripheral compared to the central ischemic core and this heterogeneity is not associated with neuronal degradation. METHODS Permanent focal ischemia was produced in 13 rats for 2.5-5 h. Brain sections were quantitatively stained for K + to assess variations in [K + ] br depletion and egress between the peripheral and central ischemic core. Reflective change and microtubule-associated protein 2 (MAP2) stained sections were used to identify the ischemic region and relate neuronal pathology to [K + ] br variations. RESULTS The mean value of normal cortex [K + ] br was 96 mEq/kg and of K + -egress in all ischemic regions over time was 12.2 mEq/kg/h, consistent with measurements from other studies. Significant differences in exaggerated K + -depletion (p<0.001) and egress (p=0.010) occurred in 56% of the peripheral compared to central ischemic core regions suggesting accelerated K + -egress from 0 to 2.5 h. Unlike [K + ] br , there was no difference between the MAP2 immunoreactivity in K + -depleted and non-K + -depleted peripheral ischemic core regions (p=0.83, p=0.16, respectively). CONCLUSIONS While confirming previous results of quantitative losses of [K + ] br in the ischemic core, we additionally show using quantitative imaging that K + dynamics within and between the peripheral and the central ischemic core are heterogeneous and not related to MAP2-assessed neuronal structural integrity. Insufficient K + in K + -depleted peripheral ischemic core regions might limit spreading depolarization-mediated infarct expansion and not allow restoration of the parenchymal membrane potential even if the functionality of the Na + ,K + -ATPase is restored. Further study of differing K + -dynamics within the ischemic core might lead to a better understanding of ischemic stroke pathophysiology.