Is Spreading Depolarization Characterized by an Abrupt, Massive Release of Gibbs Free Energy from the Human Brain Cortex?

TLDR

The cerebral cortex’s complex organization gives rise to two fundamental pathological network events—ictal epileptic activity and spreading depolarization—where the latter represents a near‑complete disruption of the physiological double Gibbs–Donnan steady state and has been observed in electrocorticographic recordings during focal ischemia and cardiac arrest. The authors propose that ion changes can be used to estimate relative changes in Gibbs free energy between physiological, ictal, and spreading depolarization states. Electrophysiological evidence shows that spreading depolarizations occur in stroke and brain trauma, and calculations indicate that the cortex releases Gibbs free energy stepwise from the physiological state through ictal activity to spreading depolarization and ultimately death, positioning spreading depolarization as a twilight state near death.

Abstract

In the evolution of the cerebral cortex, the sophisticated organization in a steady state far away from thermodynamic equilibrium has produced the side effect of two fundamental pathological network events: ictal epileptic activity and spreading depolarization. Ictal epileptic activity describes the partial disruption, and spreading depolarization describes the near-complete disruption of the physiological double Gibbs–Donnan steady state. The occurrence of ictal epileptic activity in patients has been known for decades. Recently, unequivocal electrophysiological evidence has been found in patients that spreading depolarizations occur abundantly in stroke and brain trauma. The authors propose that the ion changes can be taken to estimate relative changes in Gibbs free energy from state to state. The calculations suggest that in transitions from the physiological state to ictal epileptic activity to spreading depolarization to death, the cortex releases Gibbs free energy in a stepwise fashion. Spreading depolarization thus appears as a twilight state close to death. Consistently, electrocorticographic recordings in the core of focal ischemia or after cardiac arrest display a smooth transition from the initial spreading depolarization component to the later ultraslow negative potential, which is assumed to reflect processes in cellular death.