Donnan Equilibrium Research Articles

Recovery of dyes and salts from highly concentrated (dye and salt) mixed water using nano-filtration ceramic membranes

In this study, a higher concentration of (reactive dyestuff and salt) mixed water was used to verify the feasibility of separation by membrane techniques. The commercial nano filtration ceramic membrane (MWCO 200 Da) has been used in cross flow mode for separation of dyes and salts from highly concentrated mixed water solution. NF ceramic membrane presents good permeability (pure water flux 54.15 Lm−2 h−1, TMP 8 bar), 8% dye rejection and reduced salt rejection of NaCl (<8%) and Na2SO4 (<25%). Consequently, the operation parameters (TMP, temperature) and solution environment (solution pH, salt concentration and dye concentration) have been intensively evaluated for separation efficiency in the NF ceramic membrane process. Significantly, the NF ceramic membrane has performed less rejection to chloride ions than sulphate ions due to the Donnan effect. Solution pH, concentration of salt and dye concentration have shown significant effects on ceramic membrane separation performance. In addition, pollutant removals were achieved with noteworthy values for the chemical oxygen demand for permeate solution also color difference between concentrate and permeate. In conclusion, the strong rejection of dyes by the NF ceramic membranes proves that it can be suitable alternatives for textile wastewater treatment process.

Salt Effect on Donnan Equilibrium in Montmorillonite Demonstrated with Molecular Dynamics Simulations.

Donnan equilibrium governs the distribution of ions in many systems such as ion exchange membranes and biological cells in contact with an external electrolyte. Herein, Donnan equilibrium between bulk salt solution and bihydrated montmorillonite was investigated because such a system is of great importance for many nuclear waste disposal concepts. Specifically, we used molecular dynamics simulations to determine the partition coefficient of chloride, which was achieved by calculating the free-energy difference of chloride in the interlayer and the bulk using enhanced sampling methodology. Montmorillonite in equilibrium with either NaCl or CaCl2 was examined to elucidate the general difference between 1:1 and 2:1 salts. The concentration dependence of the partition coefficient for each salt was determined using three and four concentrations for NaCl and CaCl2, respectively. In the case of NaCl, we found that the partition coefficient increased linearly with the concentration, while for CaCl2, the increase was proportional to the square root of the concentration. A derivation of the partition coefficient using general Donnan theory that includes excess free energy contributions beyond the electrostatic Donnan potential is also presented. For both salts, the agreement between the partition coefficient from the simulations and Donnan theory was excellent. Although Donnan theory is a continuum theory derived without any reference to atomistic details, the present results justify its application to systems with nanoscale pores.

Transport properties of graphene oxide nanofiltration membranes: Electrokinetic modeling and experimental validation

AbstractThere is a need for developing reliable models for water and solute transport in graphene oxide (GO) membranes for advancing their emerging industrial water processing applications. In this direction, we develop predictive transport models for GO and reduced‐GO (rGO) membranes over a wide solute concentration range (0.01–0.5 M) and compositions, based on the extended Nernst–Planck transport equations, Donnan equilibrium condition, and solute adsorption models. Some model parameters are obtained by fitting experimental permeation data for water and unary (single‐component) aqueous solutions. The model is validated by predicting experimental permeation behavior in binary solutions, which display very different characteristics. Sensitivity analysis of salt rejections as a function of membrane design parameters (pore size and membrane charge density) allows us to infer design targets to achieve high salt rejections. Such models will be useful in accelerating structure‐separation property relationships of GO membranes and for separation process design and optimization.

A scenario for the origin of life: Volume regulation by bacteriorhodopsin required extremely voltage sensitive Na-channels and very selective K-channels.

The osmotic activity produced by internal, non-permeable, anionic nucleic acids and metabolites causes a persistent and life-threatening cell swelling, or cellular edema, produced by the Gibbs-Donnan effect. This evolutionary-critical osmotic challenge must have been resolved by LUCA or its ancestors, but we lack a cell-physiology look into the biophysical constraints to the solutions. Like mycoplasma, early cells conceivably preserved their volume with Cl- , Na+ , and K+ -channels, Na+ /H+ -exchangers, and a light-dependent bacteriorhodopsin-like H+ -pump. Here, I simulated protocells having these ionic-permeabilities and inhabiting an oceanic pond before the Great-Oxygenation-Event. Protocells showed better volume control and stable resting potentials at lower external pH and higher temperatures, favoring a certain type of extremophile life. Prevention of Na+ -influx at night, with low bacteriorhodopsin activity, required deep shutdown of highly voltage-sensitive Na+ -channels and extremely selective K+ -channels, two conserved features essential for modern neuronal encoding. The Gibbs-Donnan effect universality implies that extraterrestrial cells, if they exist, may reveal similar volume-controlling mechanisms.

Influence of ligand density variations on the two peak elution behavior of a monoclonal antibody in cation exchange chromatography

Cation exchange chromatography, as part of the monoclonal antibody purification train, is known as a mild polishing technique. However, in the last couple of years, more and more publications have shown unusual elution behavior, resulting from e.g. on-column (reversible) unfolding and aggregation of the predominantly mAb molecules. The stability of the investigated protein seems to play a significant role in this phenomenon. We have used a glycosylated IgG1 antibody as a model protein and investigated several influencing factors, including pH value and ligand density variations of three prototype Fractogel® cation exchange resins. Ligand density, pH and salt concentration are the main contributing factors in the Donnan effect, i.e. distribution of ions, between resin pore volume and bulk volume. This leads to a significantly lower pH value the protein is subjected to during the on-column hold time and therefore influences the conformational stability of our protein. Nano-DSF and kinetic SEC measurements show that the protein is destabilized at low pH values, but also, that the binding to the CEX resin and the elution with increasing salt concentration is responsible for the resulting two-peak elution behavior and partially reversible unfolding and aggregation.

Dual-electric layer nanofiltration membranes based on polyphenol/PEI interlayer for highly efficient Mg2+/Li+ separation

In recent years, the global demand for lithium resources has grown substantially due to the rapid development of the new energy industry. The nanofiltration (NF) technique is a feasible method to extract lithium from salt-lake brine, and the high Mg2+/Li+ separation selectivity of the NF membrane is the crucial factor in the NF separation process. In this work, the polyamide (PA) layer was prepared on the polyphenol/PEI interlayer-modified polysulfone (PSF) substrate to endow the NF membrane with decreased pore size and weakened electronegativity. Enhanced steric hindrance effect and reduced electrostatic attraction between Mg2+ and PA layer increased the Mg2+ rejection, thereby improving the Mg2+/Li+ separation factor of the NF membrane. Furthermore, the positively charged polyphenol/PEI interlayer hindered the permeation of Mg2+ through the Donnan effect, further enhancing the Mg2+/Li + separation factor. A separation factor up to 50.7 for Mg2+/Li+ was achieved by extracting lithium from simulated brine using the obtained NF membrane. In addition, the NF membrane exhibited a permeability of 18.6 L m−2 h−1·bar−1 and excellent long-term stability, which greatly improved the Mg2+/Li+ separation efficiency and reduced energy consumption. Therefore, this work provides a simple strategy for preparing NF membranes with high Mg2+/Li+ separation factor and permeability.

Aliphatic polyamide nanofilm with ordered nanostripe, synergistic pore size and charge density for the enhancement of cation sieving

Enhanced cation sieving selectivity is significant for polyamide (PA) nanofiltration membrane in terms of extracting lithium from Salt Lake brines, which enable to reduce production cost and operating energy consumption. Herein, an aliphatic PA nanofilm with ordered nanostripe was fabricated using a novel distorted and non-coplanar monomer, cyclopentane tetracarboxylic acid chloride (CPTC). Because of the fine-tuning of the dendrimer porous layer, the resultant aliphatic PA membrane revealed decreased thickness in separation layer, and an enhanced synergistic effect of size exclusion and Donnan equilibrium on mono-/divalent cation. Separation experiments indicated that a higher MgCl2 rejection (up to 98.36%) and a lower LiCl rejection (33.3%) were obtained, thus achieving a good cation selectivity (48.25 for Na+/Mg2+, 36.5 for Li+/Mg2+). This result was better compared with the full-aromatic and most of the literature reported positive charged PA membranes. Moreover, water flux of the CPTC–tris(2-aminoethyl) amine (TAEA) membrane with nanostripe structure (N-CPTC–TAEA) increased 3.98–4.74 times (for example, 135.9 ± 4.62 for 2000 ppm LiCl) that of the CPTC–TAEA membrane. Meanwhile, the N-CPTC–TAEA also exhibited a better antifouling property than that of the full-aromatic membrane. This study demonstrates that the N-CPTC–TAEA tends to be an alternative membrane material for cation separation.

Mechanisms of Blood pH Changes in Venovenous Extracorporeal Membrane Systems: Roles of Hemoglobin-Ion Binding and Donnan Equilibrium.

An equilibrium model was developed to understand interrelated, physicochemical mechanisms leading to blood pH and electrolyte distribution changes in patients because of venovenous extracorporeal membrane oxygenation (ECMO) and carbon dioxide removal. The model consists of plasma and red cell compartments between which water and small ions can move to establish an equilibrium state. Governing forces are as follows: 1) ionic electroneutrality in each compartment; 2) osmotic equilibrium between compartments; 3) mass balance of small ions other than bicarbonate; 4) oxygen (O 2 )-dependent hemoglobin (Hb)-Cl binding in red cells; 5) albumin binding to Cl - , Ca 2+ , and Mg 2+ in plasma; and 6) chemical equilibria of carbonates and phosphates in each compartment. The model was constructed and validated using recent clinical ECMO inlet and exit blood-pH and electrolyte concentration data. The model closely described pH and electrolyte concentration changes in both states, which validated the model. The model was then used to predict CO 2 and O 2 saturation-induced changes in pH and electrolyte concentrations. It was found that O 2 -dependent Hb-Cl binding had a much lesser effect on blood acid-base status changes and electrolyte shifts during ECMO than previously thought. The model showed that the Cl-shift and Gibbs-Donnan equilibrium effects, characterized by pH and electrolyte distribution changes during ECMO, were primarily caused by changes in pH-induced electrical charge on mainly Hb and other constrained ions in red cells. These insights can improve understanding of the same factors acting when blood traverses the lung.

Transport of Ligand Coordinated Iron and Chromium through Cation-Exchange Membranes

Fluxes of negatively charged ligand-coordinated iron, Fe(CN)6 3/4-, and chromium, CrPDTA1/2−, through two promising commercial cation-exchange membranes, Aquivion E87–05S and Fumasep E-620(K), were measured as functions of current density. The magnitude of the partial current density reached a maximum of μA cm−2 at the maximum applied current density magnitude of mA cm−2 for Fe(CN)6 3/4− transport through Aquivion, or 0.1% of the total current density. Fumasep E-620(K) blocks practically all crossover of both compounds. Both membranes sorb more Fe(CN)6 3/4− and CrPDTA1/2− than predicted by Donnan equilibrium, and low crossover rates can be attributed mainly to slow diffusion, not charge-based rejection of co-ions. The magnitude of the diffusion coefficient appears to correlate with hydraulic permeability. Although Aquivion E87–05S and Fumasep E-620(K) have significant and observable differences in membrane crossover rates, cells built with the DI-soaked membranes offer similarly high coulombic efficiency, indicating the relatively small contribution that crossover makes to inefficiency over a single cycle.

Preparation of a GO/PB-modified nanofiltration membrane for removal of radioactive cesium and strontium from water

In this study, a novel modified nanofiltration (NF) membrane was fabricated to treat radionuclide-contaminated water by incorporation of Prussian blue (PB), graphene oxide (GO) and polyethylene glycol (PEG) into polysulfone (PSf) substrate. In this work, PB provided a large number of adsorption sites for the membrane, GO improved the Donnan effect of the polyamide (PA) layer by enhancing the negative charge, and PEG promoted the uniform dispersion of PB through interparticle electrostatic interaction and steric hindrance while increasing the adsorption sites on the surface of channels in the substrate by adjusting the pore structure. A conceptual model for the role of substrate in interfacial polymerization was then proposed. The modified membrane achieved efficient rejection of cesium (Cs+, 99.5%) and strontium (Sr2+, 97.5%). Its Cs+ rejection rate still remained high (about 96%) even in the treatment of natural surface water containing various inorganic salts and organic matters. What’s more, the modified membrane exhibited excellent stability in both strong acid solutions and long-term operation. Then, potassium chloride (KCl) solution was applied to regenerate the modified membrane, which achieved high generation rate as compared to traditional acid regenerants. The excellent filtration performance inferred that the novel GO/PB-modified NF membrane holds great application potential for the application of simultaneous removal of radioactive Cs+ and Sr2+ from contaminated water.

Preparation of highly permeable electropositive nanofiltration membranes using quaternized polyethyleneimine for dye wastewater treatment

To solve water pollution induced by the electropositive dyeing wastewater, in this study, a loose electropositive nanofiltration (NF) membrane is prepared by the interfacial polymerization between self-prepared quaternized polyethyleneimine (QPEI) and 1,3,5-benzenetricarbonyl trichloride (TMC). Here the QPEI reduces the amine groups required for interfacial polymerization with high Zeta potential at the membrane surface. Meanwhile, the crosslinking reaction between QPEI and TMC is limited by steric hindrance effect, thus achieving a loose structure of the NF membranes. The obtained quaternized polyethyleneimine nanofiltration membranes (NF-QPEI) show a high selectivity based on Donnan effect. Rejections of divalent cations and common dyes are higher than 98%, with the excellent water flux of 8.21 L·m−2·h−1·bar−1. Also, the membrane shows high operation stability for 36 h in dye separation test. Therefore, this work can provide a new strategy for the preparation of the electropositive NF membranes in term of dyeing wastewater separation.

Boundary-Monte Carlo Method for Neutral and Charged Confined Fluids

In this work, we describe a new Monte Carlo (MC) simulation method to investigate highly coupled fluids in confined geometries at a constant chemical potential. This method is based on so-called multi-scale Hamiltonian methods, wherein the chemical potential is determined using a more amenable Hamiltonian for a fluid in an "outer" region, which facilitates standard methods, such as grand canonical MC simulations or Widom's particle insertion method. The (inner region) fluid of interest is placed in diffusive contact with the simpler outer fluid via a boundary zone wherein the Hamiltonian is transformed. The current method utilizes an ideal fluid for the outer regions, which allows for implicit rather than explicit simulations. Only the boundary and inner region need explicit consideration; hence, the nomenclature used is boundary-Monte Carlo. We illustrate the utility of the method for simple neutral and charged fluids in cylindrical and planar pores. In the latter case, we use a dense room-temperature ionic liquid model and illustrate how the boundary zone establishes a proper Donnan equilibrium between inner and outer fluids in the presence of charged planar electrodes. Thus, the method allows direct calculation of properties such as the differential capacitance, without the need for additional difficult calculations of the requisite Donnan potential.

Cu2+/alginate nanofiltration membranes fabricated at the aqueous contra-diffusion “interface” for salt/dye rejection

Thin-film composite (TFC) membranes can find broad uses in desalination and wastewater treatment. However, industrialized interfacial polymerization involves many organic solvents and toxic monomers. An aqueous fabrication process can meet the standards of green and sustainable production, but fabricating defect-free thin films in a homogenous phase remains challenging. Herein, we fabricate a series of TFC nanofiltration membranes through a contra-diffusion process based on the cross-linking of metal ions and alginate. The film formation is confined at the ultrafiltration substrate surface due to the competition between reaction and restricted diffusion. Among a series of metal ion/alginate composites, the Cu2+/alginate composite membrane displays superior nanofiltration performance because of the strong affinity between Cu2+ and alginate. The highly negatively charged membrane performs a high rejection to divalent anions and anionic dyes based on the Donnan effect. The effects of alginate concentration and diffusion time on membrane performance were investigated to achieve optimal fabrication conditions. The as-prepared membrane shows a rejection of 96.2% to Na2SO4 with permeation flux around 50.2 L·m−2·h−1 under 0.6 MPa, and 99.5% to several dye molecules. Moreover, the membrane performs outstanding anti-fouling and anti-bacterial properties because of its excellent hydrophilicity and the existence of Cu2+.

Layer-by-layer (LBL) hollow fiber nanofiltration membranes for seawater treatment: Ion rejection

Layer by layer (LBL) hollow fiber nanofiltration (NF) membranes assembled by poly(styrene sulfonate) (PSS)/poly(allylamine) (PAH) with 2.5 bilayers, both uncrosslinked (PSS/PAH)2.5 and crosslinked (PSS/PAH)2.5-X, were researched as a pretreatment for seawater. Focusing on the stability and ion rejections, PSS/PAH NF membrane demonstrated long time stable ion rejection after exposure in artificial seawater (ASW, >300 h) and a unique ion rejection behavior. Overcompensation of PAH contributed to the excess cationic amine groups in LBL layers. This explains the high rejection of bivalent cations, Mg2+, Ca2+ and Sr2+, for both membranes size exclusion and Donnan effect for single salt feed. The extrinsic compensation of SO42− to cationic amine groups for (PSS/PAH)2.5 resulted in unexpected lower rejection of SO42− than Cl−. In ASW, increased rejection to SO42− and reduced rejection to Cl−, bivalent and monovalent cations caused by the extrinsic compensation of Cl− to the amine groups highlighted the dominance of the affinity or sorption effect over the size and Donnan effect. A coherent ion rejection mechanism incorporating anion extrinsic compensation, combined with the size and Donnan exclusion, constitutes the third dimension for ion transport across LBL membranes.

Donnan equilibrium revisited: Coupling between ion concentrations, osmotic pressure, and donnan potential

This paper discusses the little-known fact that Donnan’s equilibrium criteria established over 100 years ago neglected the coupling between ion concentrations and the osmotic pressure. Such coupling can be treated based on general thermodynamic considerations including the solvent equilibrium, leading to a membrane potential that consists of not only the classical Donnan potential term but also an additional term due to the osmotic pressure, and the existence of a membrane potential even when the impermeable species are not charged. This coupled treatment conflicts with the well-established Poisson–Boltzmann equation and Nernst–Planck equation, but is consistent with the extension of these equations including the solvent effects by Freise and Schlogl, enables us to view the electrical double layer equilibrium as Donnan equilibrium.

Modeling the Gibbs–Donnan effect during ultrafiltration and diafiltration processes using the Poisson–Boltzmann theory in combination with a basic Stern model

The Gibbs–Donnan effect is a well-known phenomenon causing ions to be distributed unevenly across semi-permeable membranes that are permeable to ions but not to larger macromolecules such as proteins. In protein ultrafiltration and diafiltration (UF/DF) processes, this effect often leads to discrepancies between the pH and excipient concentrations in the final drug substance and in the DF buffer. In this work, a model describing the retentate and permeate composition throughout combined UF/DF processes is introduced. The model accounts for volume exclusion effects and electrostatic interactions between ions and the protein based on the Poisson–Boltzmann theory in combination with a basic Stern model. Advantages and limitations of the proposed model were analyzed using UF/DF experiments with multiple diafiltration buffers and proteins. A comparison between simulated and experimental permeate data showed good agreement for low to moderate Donnan potentials but model limitations for high Donnan potentials at protein concentration larger 100 gL -1 . In contrast, simulated retentate data showed good agreement for both low and high Donnan potentials and for protein concentrations up to 190 gL -1 . It was demonstrated that in this high protein concentration regime, the applied basic Stern model provides more accurate predictions compared to previous theories based on the Poisson–Boltzmann theory alone. This makes the model a valuable tool to describe discrepancies between pH and excipient concentrations in the final drug substance and DF buffer for highly concentrated protein formulations. As model predictions are based solely on structural information on the protein and the composition of the DF buffer, the model is particularly beneficial at an early stage in process development to streamline process development and improve process understanding. • Introduction of a model to describe the Gibbs–Donnan effect in UF/DF processes. • Advanced implementation of the cell model approximation. • Calibration solely based on structural information on the protein. • Validation using various proteins (up to 190 g/L) and buffer systems.

Facile strategy for preparing a novel reinforced blend membrane with high cycling stability for vanadium redox flow batteries

• The ether-free backbone and acid-base interaction greatly improve the structural stability of the acid-base blend membrane. • The acid-base interaction and Donnan effect contribute to the superb ion selectivity of the blend membrane. • The membrane exhibits a remarkable cycling stability with high performance in VRFB. Herein, to resolve issues regarding the long-term stability of cost-effective non-fluorinated membranes for Vanadium redox flow batteries (VRFBs), we design a facile strategy for fabricating a composite membrane based on long-side-chain Sulfonated poly(terphenylene) (SPTP) blended with Polybenzimidazole (PBI). The introduction of PBI in the ether-free SPTP matrix effectively mitigates the transportation of vanadium ions owing to the Donnan repelling effect and the low swelling ratio of the membranes caused by the acid-base interactions between the imidazolium and sulfonic groups. 1 H NMR and XPS spectra confirm the chemical structure of the prepared membranes. The optimized membrane achieves a lower area resistance, of 0.34 Ω cm 2 , as well as a low vanadium permeability, of 1.62 × 10 −8 cm 2 min −1 , in comparison to that of Nafion117 (0.4 Ω cm 2 and 4.2 × 10 −7 cm 2 min −1 ). Consequently, VRFBs that utilize such membranes exhibit superior coulombic and energy efficiencies—of 99.5% and 86.2% at 100 mA cm −2 , respectively—which are an improvement on those of Nafion117 (at 96.1% and 80.9%, respectively). It is important to note that the ether-free backbone, electrostatic repulsion, and reinforcement of PBI greatly improve the mechanical and chemical stability of the blend membranes. Therefore, the C8 membrane presents excellent cycling stability, of up to 1500 charge–discharge cycles, with no significant attenuation in the CE/EE under strong acidic and oxidizing conditions, demonstrating its high physicochemical stability. The results of this study indicate that the SPTP/PBI blend membranes exhibit promising prospects for application in VRFBs.

The Influence of Current Density on Transport of Vanadium Acetylacetonate through a Cation-Exchange Membrane

Fluxes of negatively charged, neutral, and positively charged vanadium acetylacetonates through the cation-exchange membrane Nafion® 211 were measured as functions of current density. Fluxes increase in order V(C5H7O2)3 − < V(C5H7O2)3 0 < V(C5H7O2)3 + as expected for a membrane with fixed negative charges. Furthermore, the dependence of these fluxes on current density is quantitatively consistent with predictions made using independently measured conductivities in Nernst-Planck-Einstein transport equations. However, differences between the three fluxes are smaller than predicted by Donnan equilibrium calculations for Nafion 211 immersed in V(C5H7O2)3 solutions. Specific interactions between sorbed species appear to be responsible for the relatively rapid transport of V(C5H7O2)3 − compared to V(C5H7O2)3 +.

Partially Reduced Graphene Oxide Membranes Crosslinked by an Anionic Porphyrin: Green Fabrication for High‐Performance Ion Sieving

AbstractGO membranes crosslinked by planar cation (e. g. TMPyP, a cationic porphyrin) meet the requirements of green fabrication, because TMPyP can pre‐assemble on GO sheets. However, their ion sieving performance are unsatisfactory. With shortened water channels, reduced graphene oxide (rGO) membranes owe high water flux, yet the retention of multivalent anions may goes down distinctly on account of Donnan effect decreasing obviously. Herein, we focus on the assembly between partially reduced graphene oxide (p‐rGO) and Anionic planar molecule (tetrasulfonic tetraphenyl porphyrin, TPPS), and then fabricate p‐rGO/TPPS composite membranes via assembling p‐rGO/TPPS sheets on base membrane. Anionic planar molecule is firstly used as crosslinking agent for graphene‐based membranes, which has the advantage of 100% atomic efficiency. The fabricated p‐rGO/TPPS membranes show better sieving performance than GO/TMPyP membranes on both side of rejection of Na2SO4 and water flux. Moreover, water flux go up to around another double though rejection decline slightly as the polyther sulfone (PES) base membrane with large surface pores is used.

Migraine Aura, Transient Ischemic Attacks, Stroke, and Dying of the Brain Share the Same Key Pathophysiological Process in Neurons Driven by Gibbs-Donnan Forces, Namely Spreading Depolarization.

Neuronal cytotoxic edema is the morphological correlate of the near-complete neuronal battery breakdown called spreading depolarization, or conversely, spreading depolarization is the electrophysiological correlate of the initial, still reversible phase of neuronal cytotoxic edema. Cytotoxic edema and spreading depolarization are thus different modalities of the same process, which represents a metastable universal reference state in the gray matter of the brain close to Gibbs–Donnan equilibrium. Different but merging sections of the spreading-depolarization continuum from short duration waves to intermediate duration waves to terminal waves occur in a plethora of clinical conditions, including migraine aura, ischemic stroke, traumatic brain injury, aneurysmal subarachnoid hemorrhage (aSAH) and delayed cerebral ischemia (DCI), spontaneous intracerebral hemorrhage, subdural hematoma, development of brain death, and the dying process during cardio circulatory arrest. Thus, spreading depolarization represents a prime and simultaneously the most neglected pathophysiological process in acute neurology. Aristides Leão postulated as early as the 1940s that the pathophysiological process in neurons underlying migraine aura is of the same nature as the pathophysiological process in neurons that occurs in response to cerebral circulatory arrest, because he assumed that spreading depolarization occurs in both conditions. With this in mind, it is not surprising that patients with migraine with aura have about a twofold increased risk of stroke, as some spreading depolarizations leading to the patient percept of migraine aura could be caused by cerebral ischemia. However, it is in the nature of spreading depolarization that it can have different etiologies and not all spreading depolarizations arise because of ischemia. Spreading depolarization is observed as a negative direct current (DC) shift and associated with different changes in spontaneous brain activity in the alternating current (AC) band of the electrocorticogram. These are non-spreading depression and spreading activity depression and epileptiform activity. The same spreading depolarization wave may be associated with different activity changes in adjacent brain regions. Here, we review the basal mechanism underlying spreading depolarization and the associated activity changes. Using original recordings in animals and patients, we illustrate that the associated changes in spontaneous activity are by no means trivial, but pose unsolved mechanistic puzzles and require proper scientific analysis.