• Johanna Flygt, Karsten Ruscher, Amanda Norberg, Anis Mir, Hermann Gram, Fredrik Clausen, and Niklas Marklund.
• 1 Department of Neuroscience, Section of Neurosurgery, Uppsala University , Uppsala, Sweden .
• J. Neurotrauma. 2018 Dec 1; 35 (23): 2837-2849.

AbstractTraumatic brain injury (TBI) commonly results in injury to the components of the white matter tracts, causing post-injury cognitive deficits. The myelin-producing oligodendrocytes (OLs) are vulnerable to TBI, although may potentially be replaced by proliferating oligodendrocyte progenitor cells (OPCs). The cytokine interleukin-1β (IL-1β) is a key mediator of the complex inflammatory response, and when neutralized in experimental TBI, behavioral outcome was improved. To evaluate the role of IL-1β on oligodendrocyte cell death and OPC proliferation, 116 adult male mice subjected to sham injury or the central fluid percussion injury (cFPI) model of traumatic axonal injury, were analyzed at two, seven, and 14 days post-injury. At 30 min post-injury, mice were randomly administered an IL-1β neutralizing or a control antibody. OPC proliferation (5-ethynyl 2'- deoxyuridine (EdU)/Olig2 co-labeling) and mature oligodendrocyte cell loss was evaluated in injured white matter tracts. Microglia/macrophages immunohistochemistry and ramification using Sholl analysis were also evaluated. Neutralizing IL-1β resulted in attenuated cell death, indicated by cleaved caspase-3 expression, and attenuated loss of mature OLs from two to seven days post-injury in brain-injured animals. IL-1β neutralization also attenuated the early, two day post-injury increase of microglia/macrophage immunoreactivity and altered their ramification. The proliferation of OPCs in brain-injured animals was not altered, however. Our data suggest that IL-1β is involved in the TBI-induced loss of OLs and early microglia/macrophage activation, although not the OPC proliferation. Attenuated oligodendrocyte cell loss may contribute to the improved behavioral outcome observed by IL-1β neutralization in this mouse model of diffuse TBI.

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