The brain consumes 20% of the body’s metabolic energy with muscles and digestive system at rest, despite being only 2% of the human body mass. The majority of the brain’s metabolic energy is dedicated to restoring ionic gradients due to neuronal activities. The delicate balance between metabolic energy supply and expenditure becomes critically strained in pathological activity of the brain such as seizure and spreading depression, during which requires massive rearrangement of ions across the plasma membrane. By incorporating for the dynamics of oxygen and cell volume with dynamic ion concentrations within an extended Hodgkin-Huxley model, we demonstrated the feasibility of a comprehensive framework encompassing a wide range of neuronal behaviors, including seizures and spreading depression. Such a unified framework for a wide range of neuronal behaviors provides substantial importance in the understanding of and potentially developing universal intervention strategies for these pathological states.