Deciphering epileptic dynamics through neurovascular coupling: Insights from a neuro-astrocytic-arteriolar computational modeling approach

Epilepsy is a common neurological disorder whose pathogenesis involves dysfunction in neurovascular coupling. However, current models still lack sufficient realism and diversity. This study investigates the pathological mechanisms of epilepsy based on the physiological process of neurovascular coupling. Our mathematical model incorporates neurons, astrocytes, and arterioles. It employs an extended Hodgkin–Huxley-type model for neuronal dynamics and a model of radius variation in smooth muscle driven by the filament sliding mechanism. Key elements such as BK and KIR potassium channels, along with signaling molecules including O2, Ca2+and NO, are integrated to simulate neuro-hemodynamic responses. The results reveal six distinct transitional firing patterns in neurons under a suitable external stimulation, along with bifurcation phenomena underlying the low-voltage fast oscillation state, tonic spiking, and bursting. Both qualitative and quantitative simulations demonstrate that neuronal activation triggers oscillatory calcium waves in astrocytes, leading to the release of vasodilators and ultimately inducing arteriole dilation. Furthermore, the study delineates the asymptotic behaviors of ionic concentration changes under conditions of ischemia, hypoxia, and astrocytic dysfunction. This multi-pathway synergistic neurovascular coupling framework provides a more comprehensive understanding of epileptic pathology.