Astrocytes - guardians of neuroprotection

Astrocytes are the most abundant cell type in the human cerebral cortex but the focus on these cell types have been far neglected. In the later years it has become apparent that they play important roles in the homeostasis of the brain and evidence now al so suggests that they are essential components at the blood brain barrier (BBB). In a very recent unpublished study, we have shown that the lactate transporter, monocarboxylate transporter 4 (MCT4) is densely concentrated in the part of the astrocyte plas ma membrane that abuts on the brain microvessels (the perivascular membrane). Considering the localization and characteristics of this transporter suggests that MCT4 may be a key mediator of excess lactate efflux from the brain. This is not only important for normal brain function but perhaps even more so during and following ischemia (stroke) and hypoxia when large amounts of lactate is produced. This future project will investigate the interplay of the different components of the blood brain barrier (BB B). Interactive proteins between astrocyte, basal lamina, endothel and pericytes will be studied as well as the actual anchoring proteins of MCT4. Such information would give key findings of components that may be a part of the disruption of the BBB follo wing pathological conditions such as stroke. It could also give us a greater understanding why lactate, a product of anaerobic metabolism, can accumulate to lethal high levels in the brain. Another key finding from the recent MCT4 study suggests that lact ate may act as a signaling molecule to couple local brain blood flow and neuronal activity in the normal brain. We wish to persue this finding in a collaboration with Professor Lauritzen (University of Copenhagen, Denmark) to investigate the physiological role of lactate to regulate blood flow in an in vivo model where neurons can be stimulated and blood flow measured simultaneously.