Abstract: Methods and compositions for treatment of, or protection from, neuropathy resulting from reperfusion injury upon reversal of an ischemic condition, comprising treatment or prophylactic treatment of the patient with an antagonist of the type 3 ryanodine receptor, such that a rise in cytosolic Ca2+ concentration is prevented. Therapeutic compositions containing dantrolene or aminodantrolene are administered to the patient to prevent a rise in cytosolic Ca2+ that would otherwise result in Ca2+-mediated neuronal damage. Treatment of ischemic optic neuropathy by this method is shown, and the methods and compositions presented are also applicable to other ischemic reperfusion neuropathies, such as stroke, reperfusion injury after TPA treatment/carotid endarterectomy, seizures, and excitotoxic retinal damage in glaucoma.