title: Astrogliosis is delayed in type 1 interleukin-1 receptor-null mice following a penetrating brain injury.
abstract: The cytokines IL-1alpha and IL-1beta are induced rapidly after insults to the CNS, and their subsequent signaling through the type 1 IL-1 receptor (IL-1R1) has been regarded as essential for a normal astroglial and microglial/macrophage response. To determine whether abrogating signaling through the IL-1R1 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-1R1. 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-1R1-null mice compared to wild type counterparts. However, the induction of chondroitin sulfate proteoglycans, tenascin, S-100B as well as glutamate transporter proteins, GLAST and GLT-1, and glutamine synthetase are independent of IL-1RI signaling. Cumulatively, our studies on gliosis in the IL-1R1-null mice indicate that abrogating IL-1R1 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-1R1 signaling to treat traumatic brain injuries. However, astroglial scar related proteins were induced irrespective of blocking IL-1R1 signaling and thus, other therapeutic strategies will be required to inhibit glial scarring.
authors.affiliation: Department of Neurology and Neuroscience, UMDNJ-New Jersey Medical School, Newark, NJ 07103, USA. linh3@umdnj.edu
authors.forename: Hsiao-Wen
authors.initials: HW
authors.lastname: Lin
authors.forename: Anirban
authors.initials: A
authors.lastname: Basu
authors.forename: Charles
authors.initials: C
authors.lastname: Druckman
authors.forename: Michael
authors.initials: M
authors.lastname: Cicchese
authors.forename: J Kyle
authors.initials: JK
authors.lastname: Krady
authors.forename: Steven W
authors.initials: SW
authors.lastname: Levison