Glia, and in particular astrocytes,

are vital in neuronal and CNS homeostasis. Increased expression of the astrocyte marker, glial fibrillary-associated protein (GFAP), implies neuroinflammation, linked with neuropathic pain and memory impairment. We determined whether 5-FU induced astrocyte activation via immune-to-CNS signaling pathways (neuronal vs humoral) and secondly, if astrocyte reactivity persisted beyond the intestinal injury. Materials and Methods: Female Dark Agouti rats (n = 8) were randomly allocated to saline control or 5-FU (i.p. 150 mg/kg) groups and tissues collected at either injury peak (day 3) or recovery (day 5). Western Blot analysis of hippocampal and thoracic sections determined GFAP and Interleukin-1

beta (IL-1β) expression. Myeloperoxidase (MPO) assay quantified intestinal inflammation. Statistical comparisons were conducted using GW 572016 a two-way ANOVA with Tukey’s post-hoc test. All data were expressed as mean ± SEM with p < 0.05 deemed statistically significant. Results: At injury peak (day 3), the bodyweight of 5-FU treated www.selleckchem.com/products/Methazolastone.html rats was 91% that of vehicle controls (p = 0.02) and MPO activity increased by 282% in the jejunum and 213% in the ileum compared to vehicle controls (p = 0.0007 and p = 0.0003, respectively). Although hippocampal GFAP expression showed little variance (p > 0.05), interestingly thoracic GFAP expression was significantly reduced by 28% in 5-FU treated rats compared to vehicle controls at injury peak of mucositis (day 5; p = 0.04),

yet normalized during the recovery phase (day 5; p > 0.05). IL-1β expression levels remained unchanged at both time-points. Conclusions: Down-regulation of thoracic GFAP expression is associated with astrocyte dysregulation in rats with 5-FU-induced mucositis; suggesting implications for CNS homeostasis and neuronal signaling. Further studies should clarify the role of glial dysregulation in 5-FU-induced mucositis and its potential implications Niclosamide in chemotherapy-related side-effects, such as cognitive impairment and cancer-induced pain. KE FARRELL, BA GRAHAM, S KEELY, RJ CALLISTER School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW and Hunter Medical Research Institute, New Lambton Heights, NSW Introduction: Chronic abdominal pain is a common and debilitating symptom of Inflammatory Bowel Disease (IBD). Interestingly, 30–50% of patients continue to experience pain despite clinical remission. Although the mechanisms responsible for the development of chronic pain in this subset of IBD patients are unknown, there is evidence from animal studies that central nervous system (CNS) plasticity is involved1.