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. 2018 Nov 12;35(23):2837–2849. doi: 10.1089/neu.2018.5660

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© Johanna Flygt et al., 2018; Published by Mary Ann Liebert, Inc.

This Open Access article is distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.

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FIG. 1. — Attenuated oligodendrocyte cell death by neutralization of IL-1β. Compared with sham CsA animals at seven dpi (A), the expression of cleaved caspase-3 (red) expression was increased in cFPI CsA animals (B). Cell nuclei were defined by DAPI staining (blue). (C) Cleaved caspase-3 ribonucleic acid expression (red) was detected in MOG positive OLs (green) co-labeled with DAPI (blue) in cFPI CsA animals at seven dpi. (D) At two dpi, cleaved caspase-3 expression was increased in cFPI CsA animals compared with other groups (sham CsA, sham IL-1β, and cFPI IL-1β), and at seven dpi (E), this increase was significant (*p ≤ 0.05) in the brain-injured groups (cFPI CsA and cFPI IL-1β) compared with the sham-injured groups (sham CsA and sham IL-1β). Cleaved caspase-3 expression was attenuated in brain-injured animals treated with the IL-1β neutralizing antibody (*p ≤ 0.05). (F) At 14 dpi, cleaved caspase-3 expression was increased in both brain-injured groups (cFPI CsA and cFPI IL-1β, *p ≤ 0.05) compared with the sham-injured groups (sham CsA and sham IL-1β). (G) Mature CC1-positive OLs (orange) with nuclear stain DAPI (blue) in sham CsA animals at seven dpi were found throughout the external capsule (marked white area). (H) In cFPI CsA animals (example from seven dpi), there was a reduced number of mature OLs, which was attenuated by the IL-1β neutralization (I; cFPI IL-1β). (J) At two dpi, a loss of mature OLs was detected in the corpus callosum (*p ≤ 0.05) and external capsule (M; *p ≤ 0.05) of cFPI CsA animals compared with the sham CsA group. The cFPI-induced loss of mature OLs was attenuated by the IL-1β neutralization (*p ≤ 0.05). (K) At seven dpi, OL loss was still detected in the corpus callosum (*p ≤ 0.05) of the cFPI CsA group compared with the sham CsA group. (N) In the external capsule, OL loss (cFPI CsA) was still attenuated by IL-1β neutralization in the cFPI IL-1β group (*p ≤ 0.05). (L) At 14 dpi, no difference was detected in the number of OLs among the treatment groups in the corpus callosum. In the external capsule (O), however, the sham IL-1β group showed a loss of mature OL when compared with other groups (sham CsA, sham IL-1β, and cFPI IL-1β; *p ≤ 0.05). Graphs are presented as mean and standard error of the mean. OL, oligodendrocyte; cFPI, central fluid percussion injury; dpi, days post-injury; CsA, inactive control antibody against cyclosporin A, IL-1β, interleukin 1 beta; MOG, myelin-oligodendrocyte-protein; DAPI, 4',6-diamidino-2-phenylindole.