Summary-Mode-actions of the Na+-Ca2+ exchanger from genes to mechanisms to a new strategy for brain disorders were comparatively s*udlea in oxidative stress, Io tran~femed Chinese hamster ovary (CHO) cells steadily expressing the Na+-Ca2+ exchanger's gone. Ca+-efflux via an active mode of the Na+-Ca2+ exchanger was elicited by hydrogen peroxide (H2O2) after preincubation of the cell with a Ca2+-free medium, whereas Ca2+-influx via a reverse mode of the Na+-Ca2+ exchanger was dramatically evoked by H2O2 after preincuhatlon of the cell with a Ca2+ medium, as a prelude to neuronal death. Accnrding to (45Ca2+) uptake of transfected CHO cells at given time inlervals or extracelluiar Na+[Na+]. gradients, hyperbola, logarithmic and sigmoid curve equations of the Na+-Ca2+ exchanger's mode-actions were respeetively defined in the absence and the presence of H2O2. The Na+-Ca2+ exchanger's eonfornational transition in oxidative stress was dominated by adenosine triphosphate (ATP)-dependent cytoskeletal redox modification, eation-π interactions and secondary Ca2+ activation These echanisms were used to generate an intracellularly distributed tetra-cluster (named VISA931) for rescuing G-protein agonist-sensitive signal transduetion and cortico-cerebral somatosensury evoke potential (SEP) from oxidation via activating forward o0eration of the Na+-Ca2+ exchanger, the β-adrenergic and the P2-purinergic receptors, bilking Ca2+ influx and catalyzing the dismutation ol superoxide anions (O2) to H2O2, In conclusion, knowledge-bascd drug design is a new strategy for developing promising candidates of neuroprotective agents