Calpain has been implicated in excitotoxic neurode-generation, but its mechanism of action
particularly in adult brains remains unclear. We generated mutant mice lacking or
overexpressing calpastatin, the only solely calpain-specific inhibitor ever identified or
synthesized. Modulation of calpastatin expression caused no defect in the mice under
normal conditions, indicating that calpastatin functions as a negative regulator of calpain
only under pathological conditions. Kainate-evoked excitotoxicity in hippocampus resulted …