Blood-brain barrier opening to large molecules does not imply blood-brain barrier opening to small ions

► The blood-brain barrier can be open for macromolecules but closed for small ions. ► The CO2-dependent DC deflection is a functional marker for the electrical barrier. ► Extracellular potassium is a functional marker for the electrical barrier. ► Intracarotid DHC is not suitable to study the barrier as it causes focal ischemia.