The present invention provides apoaequorin-based compositions and methods for preconditioning neurons in a subject to reduce neuronal injury due to brain ischemia. Methods include the step of administering apoaequorin to neurons in a subject, wherein the apoaequorin initiates a change in cytokine expression levels resulting in a reduction of neuronal injury due to brain ischemia as compared to neurons not administered the apoaequorin. Various formulations, including injectable dosages, are described.