Recently, we determined that transfusion of a single bolus dose of nRBC expanded the therapeutic window for tPA treatment in a rat model of ischemic stroke and reduced hemorrhagic neurological injuries in a mouse TBI model. In addition, the efficacy of nRBC was dramatically increased when this drug was exchange transfused to avoid the issue of volume over load. These results support the development of nRBC as a universal neurovascular protective stroke drug to expand the number of ischemic stroke patients treatable with tPA beyond the current 2-3% achieved after 16 years of continuous clinical use. Even without tPA treatment, treatment with nRBC alone markedly reduced the infarct volume in the rat model of ischemic stroke. The neuroprotection against hemorrhagic injuries in traumatic brain injury model would suggest nRBC may be safely used to expand the golden hour in both hemorrhagic and ischemic stroke patients and can be used by first responders prior to the time consuming diagnostic neuroimaging required to distinguish between hemorrhagic stroke and ischemic stroke.