Phagocytosis of dead or dying neurons after ischaemia has generally been thought to be beneficial, as it clears harmful cellular components and decreases inflammation. However, a new study by Neher et al. shows that brain macrophages can phagocytose functional, living neurons after transient ischaemia and actually promote brain atrophy.In areas of the ischaemic brain in which the interruption of blood supply is most pronounced, rapid neuronal death ensues owing to energy depletion, but in surrounding areas, there is a delayed cell loss, which offers an opportunity for therapeutic intervention. Previous studies have shown that viable neurons exposed to toxic stimuli at sublethal levels can display the eat me' signal phosphati-dylserine (PS), which induces their phagocytosis by macrophages. After ischaemia, neurons in the peri-infarct area have been shown to display PS at levels that peak after 3 days.The PS signal is recognized by the phagocytic proteins Mer receptor tyrosine kinase (MERTK) and milk fat globule EGF-Kke factor 8 (MFGE8; also known as lactadherin), which are upregulated in brain macrophages in response to inflammation. Here, the authors showed that MERTK and MFGE8 were temporarily upregulated in rodent brain macrophages 3-7 days after transient, focal brain ischaemia and that peak expression of these proteins coincided with macrophage activation.
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