Abstract Body: Intracerebral Hemorrhagic (ICH) stroke is the second most common type of stroke and its aftermath is often more severe than ischemia. Recent population data has shown increasing trends of ICH in middle aged people, contributing to the economic burden of society. In order to improve post ICH outcome, immediate therapeutic interventions should be administered. Hence, our research is looking into the effects of electrical stimulation of the perihematomal cortex in the hyperacute/acute phase post ICH. The end goal is to test improvement in outcomes of subjects post the administration of such a stimulation paradigm by using the observations in experimental data to validate the theoretical model and hence design a closed loop stimulation paradigm. The two approaches in the work:
Experimental: Hemorrhagic stroke is induced in minipigs by injecting 2cc of blood into the ventricular space beneath sensorimotor cortex to simulate an ICH. We insert ultra flexible microelectrodes in this region to record cortical neuronal activity and administer stimulation. Neural activity (Electrophysiological) data is collected pre/post stroke and during stimulation. The data collected is analyzed to understand changes in neural activity at different points in time. Through preliminary data analysis, we could clearly see the changes in the statistics of neural activity (pre/post ICH InterSpike Interval (ISI) histogram and firing frequency histogram). Local connectivity changes were observed in the data. Further removal of stimulation artifacts and analysis of neural data before, during and after stimulation shall be performed to understand the changes that occur during stimulation.
Theoretical: We have mathematically modeled a neuron-astrocyte-vascular system in the cortical perihematoma by extending Hodgkin-Huxley biophysics to simulate pre/post acute ICH and electrical stimulation paradigms in such conditions. The results obtained help us understand the changes in the system dynamics post ICH with bifurcation analysis giving unique outlook of the complex system. The simulated data shows increase in excitability of perihematomal tissue during acute phase. Further, the model also showcases calcium ion dyshomeostasis and problems in ATP production and consumption. Normal stimulation paradigms are shown to not work in such settings. Further exploration of the intricacies of the system is at focus to better understand electrical stimulation in such cerebrovascular conditions.