Probes for INS

Traumatic 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 plausibly 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 OL 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 2, 7 and 14 days post-injury. At 30 min post-injury, mice were randomly assigned to receiving an IL-1β neutralizing or a control antibody. OPC proliferation (5-ethynyl 2´- deoxyuridine (EdU)/Olig2 co-labeling) and mature OL cell loss was evaluated in injured white matter tracts. Microglia immunohistochemistry and ramification using Sholl analysis was also evaluated. Neutralizing IL-1β resulted in attenuated cell death, indicated by cleaved caspase-3 expression, and reduced loss of mature OLs from 2-7 days post-injury in brain-injured animals. IL-1β neutralization also attenuated the early, 2 day post-injury, increase of microglial immunoreactivity and the change in their ramification. However, the proliferation of OPCs in brain-injured animals was not altered. Our data suggest that IL-1β is involved in the TBI-induced loss of OLs and early microglial 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.