Astrocyte-neuron lactate shuttle plays a pivotal role in sensory-based neuroprotection in a rat model of permanent middle cerebral artery occlusion

Abstract

AbstractWe have previously demonstrated protection from impending cortical ischemic 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 sought other complementary mechanisms that contribute to sensory-based protection. We hypothesized that astrocytes-neuron lactate shuttle (ANLS) activation could be another potential underpinning mechanism that complements collateral flow in the protection process. Supporting our hypothesis, using functional imaging, pharmacological treatments, and postmortem histology, we showed that ANLS played a pivotal role in sensory stimulation-based protection of cortex and therefore serves as the other supporting mechanism underpinning the protection process.