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Short-term effects of repeated neonatal oral sucrose treatment and pain on hippocampal and serum inflammatory cytokine levels and microglia density in mouse pups Hoq, Fermin Samara


Background: In the neonatal intensive care unit, preterm infants experience 7-17 clinically required but painful procedures daily. Oral sucrose is the standard treatment for minor procedural pain, but the combined short-term cumulative effects of sucrose treatment for pain on brain development are unknown. Using a neonatal mouse paradigm, previous studies found that during the 1st week of life, repeated pain and/or sucrose exposure impaired short-term memory and reduced regional and white matter structure volumes in adulthood, including the corpus callosum, fimbria, and the hippocampus. The objective of this study was to determine whether repeated neonatal pain and/or sucrose exposure altered pro/anti-inflammatory markers, specifically IL-1β, IL-6, and TNF-α, in hippocampal tissue and serum of 8-day old mouse pups. Hippocampal microglial density of male mouse pups was also examined. Methodology: Using a previously established neonatal mouse paradigm, neonatal mice were randomly assigned to receive water or 24% oral sucrose prior to being handled or needle-pricked, 10X/day from postnatal day (P) 1-6. Blood and hippocampal tissue were collected at P8 and assayed for various cytokines (e.g. IL-1β, IL-6, and TNF-α). In addition to cytokine levels, microglial density was assessed in the hippocampus of P8 male mice. Results: Although no sex effects were evident, a significant group effect was found for several inflammatory cytokines. Hippocampal IL-10 levels were significantly lower in sucrose + handling (p<0.01), water + handling (p<0.05), and water + needle-prick exposed mice (p<0.05) compared to controls. In serum, IL-1β levels were significantly greater in mice that were exposed to sucrose + handling compared to controls (p<0.01), sucrose + needle-prick (p<0.01), and water + needle-prick (p<0.01) groups, while mouse pups exposed to sucrose + needle-prick showed significantly lower serum IL-5 levels compared to controls (p<0.05). Preliminary microglia density descriptive analysis showed a trend suggesting that in 8-day old males, any treatment and/or intervention exposure alter microglial cell counts in the hippocampus. Conclusion: My findings add to evidence of adverse effects of neonatal repeated exposure to pain and sucrose, with implications for the use of oral sucrose for pain in clinical practice based on the neuroinflammatory responses to these early-life stressors.

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