Poster Sessions CP03: Trophic Factors. Effects of early post‐natal exposure of cerebral cortex to hyper‐IL‐6 on development and cognition in the CD‐1 mouse

Abstract

Pro‐inflammatory cytokines, especially Interleukin (IL)‐6, are elevated in the brains and serum of very premature infants in association with perinatal infectious and hypoxic/ischemic insults. To determine potential adverse effects of IL‐6 on brain development, cross‐fostered litters of male cd‐1 mice were injected subcranially with hyper‐IL‐6 or vehicle at postnatal day (pnd) 4 and examined for alterations in functional landmarks of CNS development. No acute injury response was evident at 1–7 days following hyper‐IL‐6 injection as determined by glial morphology and RNase protection assays for acute response genes, ICAM‐1, iNOS, Mac‐1, A‐20, and EB‐22. In preweanling mice, reflex ontogeny and physical markers of development were not altered; however, exposed mice demonstrated increased over‐generalized motor responses (Fox Battery) leading to an overall impression of hyper‐reactivity and hyperactivity. At pnd 24 and 80, assessment of autonomic, sensory, and motor systems (Functional Observation Battery) showed persistence of hyper‐reactivity and hyperactivity. Learning and memory were assessed by passive avoidance (PA) at pnd 24 and by radial arm maze (RAM) in adults. Hyper‐IL‐6 exposure significantly impaired PA performance. RAM performance was similar between hyper‐IL‐6 and control groups in acquisition of win‐shift task but hyper‐IL‐6 animals showed deficits on repeated acquisition task. The persistent hyperactive, hyper‐reactive behavioral phenotype evident in hyper‐IL‐6 exposed mice appeared to interfere with performance on both learning and memory tasks, suggesting that early exposure of the developing brain to IL‐6 can have persistent adverse functional effects and raising additional concerns for effects of immune mediators in premature infants.