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. 2020 May 14;127(4):466–482. doi: 10.1161/CIRCRESAHA.119.316463

Figure 5.

Figure 5.

Loss of EC-GLUT1 (endothelial glucose transporter isoform 1) leads to progressive neuronal loss, central nervous system (CNS) inflammation, and rapid lethality. A, Endothelial Glut1 expression levels (transcripts per million [TPM]) in adult mouse brain ECs, cultured brain ECs and ECs from brain, kidney, liver and lung from P7 pups as described in the Vascular Endothelial Cell Trans-omics Resource Database (VECTRDB).27 B, Schematic representation of experimental timing for brain vascular analyses in GLUT1lox/lox×Pdgfb.CreERT2 mice. C, Cerebrospinal fluid (CSF)/plasma glucose ratio in GLUT1EC−/− mice vs wild-type (WT) littermates (Student t test). D, Quantification of spontaneous movement in GLUT1EC−/− mice vs WT littermates at 1, 3, 5, and 8 days after the first tamoxifen injection (n=3 per group; repeated measures ANOVA with Sidak multiple comparisons test). E, Representative electrocorticography (ECoG) excerpts from Cre positive GLUT1lox/lox×Pdgfb.CreERT2 mice, monitored by telemetry-ECoG 24 h/day (n=3 per group) showing the baseline ECoG before the first tamoxifen injection and an aberrant ECoG 4 days after the first tamoxifen injection. F and G, Representative pictures of hippocampal (F) and of cortical (G) NeuN+ (neuronal nuclear protein)/DAPI+ neuronal nuclei in GLUT1EC−/− mice vs WT littermates >13 days after the first tamoxifen injection. H–K, Quantifications of the number of NeuN+/DAPI+ cells in the cornu ammonis 1 (CA1; H), CA3 (I), dentate gyrus (DG; J), and cortical region (K) in GLUT1EC−/− mice vs WT littermates (Student t test). L and M, Representative pictures of Iba1+ microglia (L) and GFAP+ (glial fibrillary acidic protein) astrocytes (M) in the hippocampus of GLUT1EC−/− mice vs WT littermates (n=4 per group). Quantifications show % Iba1+ and % GFAP+ area vs WT (n=4 per group; Student t test). N, Kaplan-Meier survival curve of GLUT1EC−/− mice vs WT littermates (n=8 per group; Log-rank (Mantel-Cox) test). Scale bar=500 µm for upper, 50 µm for lower (F), 50 µm (G), 100 µm (L), and 50 µm (M). *P<0.05, **P<0.01, ***P<0.001, and ****P<0.0001.