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. 2012 Feb 22;32(8):2657–2666. doi: 10.1523/JNEUROSCI.4837-11.2012

Figure 6.

Figure 6.

Inhibition of the MFG-E8 receptor reduces LPS-induced inflammatory neuronal loss. A, Neuronal loss at 3 d after LPS injection is reduced in animals coinjected with the MFG-E8 receptor (VR) antagonist, cRGD. B, LPS induces a large increase in activated microglia (stained with isolectin-B4), which is not affected by coinjection of cRGD. C, Confocal micrographs of coronal sections through the rat striatum stained for MFG-E8 (red) and microglia (isolectin-B4, green). MFG-E8-positive cells are found throughout the LPS-injected striatum, but not in the saline-injected contralateral hemisphere. MFG-E8 appears to be localized in vesicles on the microglial cell-surface (open arrows). Cells with more diffuse staining for MFG-E8 are virtually always contacted by microglia (wide filled arrows), while in animals coinjected with cRGD, MFG-E8-positive cells are isolated from microglial processes (narrow filled arrows). These cells are identified as neurons (Thy1.1). Scale bar, 5 μm for LPS high magn., 10 μm in all other pictures. D–G, Small TUNEL-positive inclusions are found throughout the LPS-injected striatum (confocal images in G). These are virtually always located inside of IB4-positive microglia (F), often colocalize with the neuronal nuclear antigen NeuN (E) and are reduced by coinjection of the VR inhibitor cRGD (D), indicating that neuronal death is executed by microglial phagocytosis. Scale bar, 20 μm. Data are means ± SEM.