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Research ArticleBasic Science Investigations

Serial Quantitative TSPO-Targeted PET Reveals Peak Microglial Activation up to 2 Weeks After an Epileptogenic Brain Insult

Mirjam Brackhan, Pablo Bascuñana, Johannes M. Postema, Tobias L. Ross, Frank M. Bengel, Marion Bankstahl and Jens P. Bankstahl
Journal of Nuclear Medicine August 2016, 57 (8) 1302-1308; DOI: https://doi.org/10.2967/jnumed.116.172494
Mirjam Brackhan
1Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany; and
2Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine, Hannover, Germany
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Pablo Bascuñana
1Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany; and
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Johannes M. Postema
1Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany; and
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Tobias L. Ross
1Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany; and
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Frank M. Bengel
1Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany; and
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Marion Bankstahl
2Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine, Hannover, Germany
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Jens P. Bankstahl
1Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany; and
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    FIGURE 1.

    (A) Representative coronal and horizontal brain images of 11C-PK11195 uptake (%ID/cm3) before and at different time points during epileptogenesis. (B) 11C-PK11195 BPND analyzed by simplified reference tissue model using cerebellar gray matter as reference. Data are mean ± SEM, with a group size of n = 4–8 per time point. Statistical analysis was performed by 1-way ANOVA and Dunnett post hoc test. *Significant differences compared with baseline (P < 0.05).

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    FIGURE 2.

    Statistical parametric mapping analysis of 11C-PK11195 uptake during epileptogenesis using SPM12 software. Coronal and horizontal t-maps resulting from comparisons of 11C-PK11195 uptake between baseline and each time point after SE (at baseline [n = 8]; at 4 h [n = 6] after SE; at 1 [n = 6], 2 [n = 5], 5, 7, 14 [n = 6, respectively], and 22 d [n = 7] after SE; and at 14–16 wk [n = 4] after SE; t test, P < 0.001, minimum cluster size of 100 voxels).

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    FIGURE 3.

    (A) Representative coronal in vitro 18F-GE180 autoradiography brain images (−3.6 mm relative to bregma) during epileptogenesis. (B) Time course of 18F-GE180 in vitro binding (Bq/pixel). Data are mean ± SEM, with a group size of n = 3–5 per time point. Statistical analysis was performed by 1-way ANOVA and Dunnett post hoc test. *Significant differences compared with baseline (P < 0.05). (C) Correlation of 11C-PK11195 in vivo BPND and 18F-GE180 in vitro binding (Pearson, P < 0.001) and correlation of 11C-PK11195 in vivo uptake and 18F-GE180 in vitro binding (Pearson, P < 0.001).

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    FIGURE 4.

    (A) Representative images of CD11b, GFAP, and NeuN staining in control and 14-d post-SE rats (CA1 region of hippocampus; insert for CD11b displays 4-times-higher magnification of pyramidal cell layer). (B) Semiquantitative evaluation of microglial and astroglial activation as well as neuronal cell loss during epileptogenesis. Data are mean ± SEM, with a group size of n = 3–5 per time point. Statistical analysis was performed by Kruskal–Wallis test and Dunn post hoc test. *Significant differences compared with baseline (P < 0.05). (C) Correlation of 11C-PK11195 in vivo BPND and immunohistochemistry scores (Spearman, P < 0.001 for CD11b and GFAP, P < 0.05 for NeuN).

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Journal of Nuclear Medicine: 57 (8)
Journal of Nuclear Medicine
Vol. 57, Issue 8
August 1, 2016
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Serial Quantitative TSPO-Targeted PET Reveals Peak Microglial Activation up to 2 Weeks After an Epileptogenic Brain Insult
Mirjam Brackhan, Pablo Bascuñana, Johannes M. Postema, Tobias L. Ross, Frank M. Bengel, Marion Bankstahl, Jens P. Bankstahl
Journal of Nuclear Medicine Aug 2016, 57 (8) 1302-1308; DOI: 10.2967/jnumed.116.172494

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Serial Quantitative TSPO-Targeted PET Reveals Peak Microglial Activation up to 2 Weeks After an Epileptogenic Brain Insult
Mirjam Brackhan, Pablo Bascuñana, Johannes M. Postema, Tobias L. Ross, Frank M. Bengel, Marion Bankstahl, Jens P. Bankstahl
Journal of Nuclear Medicine Aug 2016, 57 (8) 1302-1308; DOI: 10.2967/jnumed.116.172494
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