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

Abstract

We 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.

Involvement of Astrocytes in the Formation, Maintenance, and Function of the Blood–Brain Barrier

“…Therefore, while the amount of glucose metabolized by astrocytes varies according to the degree of brain activity, the supply of lactate to the neurons is kept almost constant thanks to its continuous release by astrocytes. This process is called astrocyte-neuron lactate shuttle (ANLS), and it seems to be especially active in association with excitatory neurotransmission [34][35][36][37][38][39][40][41][42][43][44]. It has been recently discovered that the consumption of lactate by neurons is essential for long-term memory consolidation but not, probably, for shortterm memory [45][46][47][48][49][50].…”

Selenium Nanoparticles in Protecting the Brain from Stroke: Possible Signaling and Metabolic Mechanisms

“…The result is paracrine activation of the entire astrocyte network and suppression of ischemia-induced neuronal hyperexcitation [ 74 ], likely due to lactate uptake by neurons. Since the protective effect of lactate released by astrocytes during ischemia/reoxygenation is well known [ 189 , 190 ]. A significant contribution to the protection of neurons and neighboring astrocytes can be made by the release of ATP, which, acting through the activation of P2Y and P2X purinergic receptors, can suppress ischemic neuronal hyperexcitation [ 191 ].…”