Astrogliosis is delayed in type 1 interleukin-1 receptor-null mice following a penetrating brain injury

The cytokines IL-1α and IL-1β are induced rapidly after insults to the CNS, and their subsequent signaling through the type 1 IL-1 receptor (IL-IR1) has been regarded as essential for a normal astroglial and microglial/macrophage response. To determine whether abrogating signaling through the IL-IR1 will alter the cardinal astrocytic responses to injury, we analyzed molecules characteristic of activated astrocytes in response to a penetrating stab wound in wild type mice and mice with a targeted deletion of IL-IR1. Here we show that after a stab wound injury, glial fibrillary acidic protein (GFAP) induction on a per cell basis is delayed in the IL-IR1-null mice compared to wild type counterparts. However, the induction of chondroitin sulfate proteoglycans, tenascin, S100B as well as glutamate transporter proteins, GLAST and GLT-1, and glutamine synthetase are independent of IL-IR1 signaling. Cumulatively, our studies on gliosis in the IL-IR1-null mice indicate that abrogating IL-IR1 signaling delays some responses of astroglial activation; however, many of the important neuroprotective adaptations of astrocytes to brain trauma are preserved. These data recommend the continued development of therapeutics to abrogate IL-IR1 signaling to treat traumatic brain injuries. However, astroglial scar related proteins were induced irrespective of blocking IL-IR1 signaling and thus, other therapeutic strategies will be required to inhibit glial scarring.