We have previously demonstrated protection from impending cortical stroke is achievable by sensory stimulation of the ischemic area in an adult rat model of permanent middle cerebral artery occlusion (pMCAo). We have further demonstrated that a major underpinning mechanism that is necessary for such protection is the system of collaterals among cerebral arteries that results in reperfusion of the MCA ischemic territory. However, since such collateral flow is weak, it may be necessary but not sufficient for protection and therefore we were seeking other complementary mechanisms that contribute to sensory-based protection. We hypothesized that astrocytes-to-neuron shuttle (ANLS) is another potential underpinning mechanism that could complement collateral flow in the protection process. Supporting our hypothesis, using functional imaging, pharmacological treatments, and postmortem histology, we show that ANLS has a pivotal role in sensory-based protection of cortex and therefor serves as the other supporting mechanism underpinning the protection process.