Interleukin-6 (IL-6) is a proinflammatory cytokine that is elevated acutely in the mammalian brain following infectious, traumatic and hypoxic-ischemic insults. Fetal/perinatal elevation of IL-6 in plasma and cerebrospinal fluid has been linked to hypoxic insult, premature birth, infection of fetal membranes, and maternal infection. Elevated levels of IL-6 in the premature have been associated with structural pathology identified perinatally and later in childhood. Premature birth +/- structural neuropathology has been correlated with significant cognitive and sensorimotor deficits at school age. This study will examine the effects of acute perinatal elevation of IL-6 on immediate pathology and later functional deficits. Following establishment of a mouse model, a within-litter experimental dosing design will be employed with independent measurements taken at critical times across development. Outcome measures will include structural pathology, molecular markers of development in the hippocampus and cerebellum, and functional behavioral assessments. Findings are expected to add to our understanding of inflammatory injury at a particularly sensitive period in cortical development, leading to hypotheses concerning modulation of neuroimmune responses to perinatal insults in the premature infant.
| Brunssen, Susan H; Moy, Sheryl S; Toews, Arrel D et al. (2013) Interleukin-6 (IL-6) receptor/IL-6 fusion protein (Hyper IL-6) effects on the neonatal mouse brain: possible role for IL-6 trans-signaling in brain development and functional neurobehavioral outcomes. Brain Behav Immun 27:42-53 |
