Jones, S. C. | bioRxiv Science

bioRxiv2026

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

BACKGROUNDWith 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. METHODSPermanent 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. RESULTSThe 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). CONCLUSIONSWhile 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.

neuroscience↗

bioRxiv2021

Numerical Simulation of Concussive-generated Cortical Spreading Depolarization to Optimize EEG Electrode Spacing for Non-invasive Detection

BackgroundCortical Spreading Depolarization (SD) is a propagating depolarization wave of neurons and glial cells in the cerebral gray matter. SD occurs in all forms of severe acute brain injury as documented using invasive detection methods. Based on many experimental studies of mechanical brain deformation and concussion, the occurrence of SDs in human concussion has often been hypothesized. However, this hypothesis cannot be confirmed in humans as SDs can only be detected with invasive detection methods that would require either a craniotomy or a burr hole to be performed on athletes. Typical electroencephalography (EEG) electrodes, placed on the scalp, can detect the possible presence of SD but have not been able to accurately and reliably identify SDs. MethodsTo explore the possibility of a non-invasive method to resolve this hurdle, we developed a finite element numerical model that simulates scalp voltage changes that are induced by a brain-surface SD. We then compared our simulation results with retrospectively evaluated data in aneurysmal subarachnoid hemorrhage (aSAH) patients from Drenckhahn et al. (Brain 135:853, 2012). ResultsThe ratio of peak scalp to simulated peak cortical voltage, Vscalp/Vcortex, was 0.0735, whereas the ratio from the retrospectively evaluated data was 0.0316 (0.0221, 0.0527) [median (1st quartile, 3rd quartile), n = 161, p < 0.001, one sample Wilcoxon signed rank test]. These differing values provide validation because their differences can be attributed to differences in shape between concussive- and aSAH-SDs, as well as the inherent limitations in human study voltage measurements. This simulated scalp surface potential was used to design a virtual scalp detection array. Error analysis and visual reconstruction showed that 1 cm is the optimal electrode spacing to visually identify the propagating scalp voltage from a cortical SD. Electrode spacings of 2 cm and above produce distorted images and high errors in the reconstructed image. ConclusionOur analysis suggests that concussive (and other) SDs can be detected from the scalp, which could confirm SD occurrence in human concussion, provide concussion diagnosis based on an underlying physiological mechanism, and lead to non-invasive SD detection in the setting of severe acute brain injury.

neuroscience↗