Disclosed are methods of preventing or treating neuronal damage associated with oxidative stress and/or neuronal injury. The method comprises administering to a patient a pharmaceutical composition comprising a purinergic P2Y receptor ligand, in an amount effective to increase the extracellular concentration of said agonist in the brain of the subject such that at least a portion of cell surface P2Y receptors expressed by astrocytes are activated to mount a neuroprotective response. The pharmaceutical composition may be administered orally or parenterally. The pharmaceutical composition with typically be administered to an individual within at least one hour of the event that caused oxidative stress in the subject. The pharmaceutical composition includes a P2Y purinergic receptor agonist, which can include uridine 5′-di- and triphosphate (UDP, UTP) and their analogs, adenosine 5′-diphosphate (ADP) and its analogs, cytidine 5′-di- and triphosphate (CDP, CTP) and their analogs, and dinucleoside polyphosphate compounds.
