Abstract
Introduction: Many paediatric neurological conditions have a significant inflammatory component. Post-mortem brain samples of those affected often display neuroglial irritation and the presence of inflammatory markers within the cerebrospinal fluid. The underlying molecular mechanisms behind these breakdown products are largely unknown, and further knowledge in this area would enhance treatment options and prognosis.
Methods: Using our novel pressure chamber we stimulated murine neural tissue with the inflammatory cytokines IL-1α, IL-1β, IL-6 and TNF-α to represent an inflammatory process. Subsequently we quantified the change in volume of brain samples. Inflammation was compared using established histochemical techniques and statistics were performed with ANOVA (Tukey-Kramer multiple comparisons test), using Sigma Plot 5.
Results: We demonstrated significant variation in expansion of different brain regions. Whole brain preparations demonstrated a 30% increase. The frontal (17±1.2%) and temporal (15±0.8%) lobes demonstrated the greatest susceptibility to inflammation showing significant volumetric increases over 24 hours. This can be compared to the cerebellum (7±0.6%) and brain stem (5±0.7%) volume increases. Furthermore, this inflammation was noted to be a result of aberrant signalling of the NF-κB/IKK pathway. Using standard inhibitors this inflammation could be both inhibited and reversed.
Conclusions: These results suggest that NF-κB represents a potential therapeutic target for improvement of many paediatric neurological conditions. They illustrate the varying susceptibility of different lobes of the brain and promote further research into the role of inflammation in paediatric neurology affecting these areas. Finally, we have established a novel and cost-efficient technique for quantification of neuroinflammation in a laboratory setting.
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Neilson, S., De Souza, C., Campbell, E. et al. 241 Tnf-α Induction of Infant Murine Brain Inflammation Via Ikk/Nf Kappa B Signalling: A Potential Model for Paediatric Neuroinflammation. Pediatr Res 68 (Suppl 1), 125 (2010). https://doi.org/10.1203/00006450-201011001-00241
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DOI: https://doi.org/10.1203/00006450-201011001-00241